Compressed open flow assay and use

ABSTRACT

The present invention relates to the methods, devices, and systems that make bio/chemical sensing (including, not limited to, immunoassay, nucleic assay, electrolyte analysis, etc.) faster, more sensitive, less steps, easy to perform, smaller amount of samples required, less or reduced (or no) needs for professional assistance, and/or lower cost, than many current sensing methods and devices. The present invention also allow a test performed by a smartphone.

CROSS-REFERENCING

This application claims the benefit of U.S. Provisional PatentApplication 62/456,065, filed on Feb. 7, 2017, U.S. Provisional PatentApplication 62/456,504, filed on Feb. 8, 2017, U.S. Provisional PatentApplication 62/459,972, filed on Feb. 16, 2017, and U.S. ProvisionalPatent Application 62/460,062, filed on Feb. 16, 2017, each of whichapplications are incorporated herein in their entireties for allpurposes.

INCORPORATION BY REFERENCE OF SEQUENCE LISTING PROVIDED AS A TEXT FILE

A Sequence Listing is provided herewith as a text file, “ESX18 seqlist_ST25.txt” created on November 19 and having a size of 2 KB. Thecontents of the text file are incorporated by reference herein in theirentirety.

FIELD

The present invention is related to the field of bio/chemical sampling,sensing, assays and applications.

BACKGROUND

In biological and chemical assays (e.g. diagnostic testing), often itneeds to measure the volume, change the shape, and/or detect analytes ofa sample or a part of the sample, quickly and simply, in particularlyhigh sample uniformity, which often leads to high assay accuracy. Thecurrent invention provides devices and methods for achieving thesegoals.

SUMMARY OF INVENTION

The following brief summary is not intended to include all features andaspects of the present invention. The present invention relates to themethods, devices, and systems that make bio/chemical sensing (including,not limited to, immunoassay, nucleic assay, electrolyte analysis, etc.)faster, more sensitive, less steps, easy to perform, smaller amount ofsamples required, less or reduced (or no) needs for professionalassistance, and/or lower cost, than many current sensing methods anddevices.

BRIEF DESCRIPTION OF THE DRAWINGS

The skilled artisan will understand that the drawings, described below,are for illustration purposes only. The drawings are not intended tolimit the scope of the present teachings in any way. The drawings maynot be in scale. In the figures that present experimental data points,the lines that connect the data points are for guiding a viewing of thedata only and have no other means.

FIG. 1 is an illustration of a CROF (Compressed Regulated Open Flow)embodiment. Panel (a) illustrates a first plate and a second platewherein the first plate has spacers. Panel (b) illustrates depositing asample on the first plate (shown), or the second plate (not shown), orboth (not shown) at an open configuration. Panel (c) illustrates (i)using the two plates to spread the sample (the sample flow between theplates) and reduce the sample thickness, and (ii) using the spacers andthe plate to regulate the sample thickness at the closed configuration.The inner surface of each plate may have one or a plurality of bindingsites and or storage sites (not shown).

FIG. 2 illustrates plates with a binding site or a storage site. Panel(a) illustrates a plate having a binding site. Panel (b) illustrates aplate having a reagent storage site. Panel (c) illustrates a first platehaving a binding site and a second plate having a reagent storage site.Panel (d) illustrates a plate having multiple sites (binding sitesand/or storage site).

FIG. 3 is a flow-chart and schematic of a method for reducing assayincubation time by reducing sample thickness. Panel (a) illustrates afirst plate that has at least one binding site on a substrate surface.Panel (b) illustrates a second plate (which may have a different sizefrom the first plate). Panel (c) illustrates depositing a sample(containing target binding entity) on the substrate surface (shown) orthe cover plate (not shown), or both (not shown). Panel (d) illustratesmoving the first and second plates so that they are facing each other,and reducing the sample thickness by reducing the spacing of the innerspace between the plates. The reduced thickness sample is incubated. Thereduced sample thickness speeds up the incubation time. Some embodimentof the method uses spacers to regulate the spacing, which (spacers) arenot shown in the illustration.

FIG. 4 shows reducing binding or mixing time by reducing the samplethickness using two pates, spacers, and compression (shown incross-section). Panel (a) illustrates reducing the time for bindingentities in a sample to a binding site on a solid surface (X−(Volume toSurface)). Panel (b) illustrates reducing the time for binding entities(e.g. reagent) stored on a surface of plate to a binding site on asurface of another surface (X−(Surface to Surface)). Panel (c)illustrates reducing the time for adding reagents stored on a surface ofa plate into a sample that is sandwiched between the plate and otherplate (X−(Surface to Volume)).

FIG. 5 shows how to avoid or reduce local bending in a flexible plate.Panel (a) illustrates if the inter-spacer distance is too large for aflexible plate (the second plate, e.g. a plastic film) under a given setof sample and compress conditions, the plate has, at the closedconfiguration, a local sag (i.e. bending inward) between the twoneighboring pacers, assuming the first plate is rigid. The samplebetween the plates is not drawn. Panel (b) illustrates local bending(sag) in a flexible plate in panel (a) is reduced or virtually avoidedby using a proper inter-spacer distance and a proper compression force.The sample between the plates is not drawn.

FIG. 6 illustrates reducing effect of large dust on the plate spacing(sample thickness) regulation. Panel (a) illustrates When using tworigid plates, a dust with a thickness larger than a spacer height candestroy an intended plate spacing regulation by the spacers (hencedestroy the intended sample thickness regulation). The sample betweenthe plates is not drawn. Panel (b) illustrates using a proper flexibleplate and a proper inter-spacer distance, the effect of a dust isisolated to a small area around dust, while in other areas, the platespacing (hence the sample thickness) is regulated by the spacers not thedust. This illustration has the first plate is rigid, the second plateis flexible, and the spacers are initially fixed on the first plate.Panel (c) illustrates an illustration of using a proper flexible plateand a proper inter-spacer distance, the effect of a dust is isolated toa small area around dust, while in other areas, the plate spacing (hencethe sample thickness) is regulated by the spacers not the dust. Thisillustration has the first plate is rigid, the second plate is flexible,and the spacers are initially fixed on the second plate.

FIG. 7 illustrates reducing effects of surface flatness variation ofplate by using proper spacer arrangement and flexible plate(s). Panel(a) shows that surface flatness variation can be significantly largecompared with a desired sample thickness, causing errors in determininga sample thickness. In this illustration, only one plate has a largeflatness variation (in reality, both plates may have large flatnessvariation). The sample between the plates is not drawn. Panel (b)illustrates a surface flatness variation distance of a plate, □□, is thedistance from a local maximum to a neighboring local minimum of asurface height. Panel (c) illustrates how a small surface flatnessvariation can be achieved by making one or both plate flexible and usinga proper inter-spacer distance and proper compressing force to correct,at the closed configuration, the original surface flatness variation ofthe plate when they are at open configuration. The sample between theplates is not drawn. Panel (d) illustrates making the sample thicknessvariation less than the initial surface flatness variation of the plateby using a flexible second plate and a proper inter spacer distance. Theflexible plate follows the contour of the rigid plate. The samplebetween the plates is not drawn.

FIG. 8 Spacers on a plate. Top view of photograph of (a) 46 um×46 umpillar spacer size and 54 um inter pillar distance, and (b) 10 um×70 umpillar spacer size and 10 um pillar distance; and prospect view SEM of(c) 30 um×40 um pillar spacer size of 2 um spacer height, and (d) 30um×40 um pillar spacer size of 30 um spacer height.

FIG. 9. An illustration of certain aspects of an exemplary device andmethods of collecting exhaled breath condensate (EBC) using a SiEBCA(Single-drop EBC Collector/Analyzer).

FIG. 10. An illustration of a SiEBCA with both “open spacer” and“enclosed spacer”, where the open spacer is a post (pillar) while theenclosed spacer is a ring spacer (d) and a four-chamber grid spacer (e).

FIG. 11. The surface wetting properties for an untreated and a treated(for better wetting than untreated surface) surface of a collectionplate.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The following detailed description illustrates some embodiments of theinvention by way of example and not by way of limitation. The sectionheadings and any subtitles used herein are for organizational purposesonly and are not to be construed as limiting the subject matterdescribed in any way. The contents under a section heading and/orsubtitle are not limited to the section heading and/or subtitle, butapply to the entire description of the present invention.

The citation of any publication is for its disclosure prior to thefiling date and should not be construed as an admission that the presentclaims are not entitled to antedate such publication by virtue of priorinvention. Further, the dates of publication provided can be differentfrom the actual publication dates which can need to be independentlyconfirmed.

Compressed Regulated Open Flow” (CROF)

In assaying, a manipulation of a sample or a reagent can lead toimprovements in the assaying. The manipulation includes, but not limitedto, manipulating the geometric shape and location of a sample and/or areagent, a mixing or a binding of a sample and a reagent, and a contactarea of a sample of reagent to a plate.

Many embodiments of the present invention manipulate the geometric size,location, contact areas, and mixing of a sample and/or a reagent using amethod, termed “compressed regulated open flow (CROF)”, and a devicethat performs CROF.

The term “compressed open flow (COF)” refers to a method that changesthe shape of a flowable sample deposited on a plate by (i) placing otherplate on top of at least a part of the sample and (ii) then compressingthe sample between two plates by pushing the two plates towards eachother; wherein the compression reduces a thickness of at least a part ofthe sample and makes the sample flow into open spaces between theplates.

The term “compressed regulated open flow” or “CROF” (or “self-calibratedcompressed open flow” or “SCOF” or “SCCOF”) refers to a particular typeof COF, wherein the final thickness of a part or entire sample after thecompression is “regulated” by spacers, wherein the spacers, that areplaced between the two plates.

The term “the final thickness of a part or entire sample is regulated byspacers” in a CROF means that during a CROF, once a specific samplethickness is reached, the relative movement of the two plates and hencethe change of sample thickness stop, wherein the specific thickness isdetermined by the spacer.

One embodiment of the method of CROF, as illustrated in FIG. 1,comprises:

(a) obtaining a sample, that is flowable;

(b) obtaining a first plate and a second plate that are movable relativeto each other into different configurations, wherein each plate has asample contact surface that is substantially planar, wherein one or bothof the plates comprise spacers and the spacers have a predeterminedheight, and the spacers are on a respective sample contacting surface;

(c) depositing, when the plates are configured in an open configuration,the sample on one or both of the plates; wherein the open configurationis a configuration in which the two plates are either partially orcompletely separated apart and the spacing between the plates is notregulated by the spacers; and

(d) after (c), spreading the sample by bringing the plates into a closedconfiguration, wherein, in the closed configuration: the plates arefacing each other, the spacers and a relevant volume of the sample arebetween the plates, the thickness of the relevant volume of the sampleis regulated by the plates and the spacers, wherein the relevant volumeis at least a portion of an entire volume of the sample, and whereinduring the sample spreading, the sample flows laterally between the twoplates.

The term “plate” refers to, unless being specified otherwise, the plateused in a CROF process, which a solid that has a surface that can beused, together with another plate, to compress a sample placed betweenthe two plate to reduce a thickness of the sample.

The term “the plates” or “the pair of the plates” refers to the twoplates in a CROF process.

The term “first plate” or “second plate” refers to the plate use in aCROF process.

The term “the plates are facing each other” refers to the cases where apair of plates are at least partially facing each other.

The term “spacers” or “stoppers” refers to, unless stated otherwise, themechanical objects that set, when being placed between two plates, alimit on the minimum spacing between the two plates that can be reachedwhen compressing the two plates together. Namely, in the compressing,the spacers will stop the relative movement of the two plates to preventthe plate spacing becoming less than a preset (i.e. predetermined)value. There are two types of the spacers: “open-spacers” and“enclosed-spacers”.

The term “open-spacer” means the spacer have a shape that allows aliquid to flow around the entire perimeter of the spacer and flow passthe spacer. For example, a pillar is an open spacer.

The term of “enclosed spacer” means the spacer of having a shape that aliquid cannot flow abound the entire perimeter of the spacer and cannotflow pass the spacer. For example, a ring shape spacer is an enclosedspacer for a liquid inside the ring, where the liquid inside the ringspacer remains inside the ring and cannot go to outside (outsideperimeter).

The term “a spacer has a predetermined height” and “spacers havepredetermined inter-spacer distance” means, respectively, that the valueof the spacer height and the inter spacer distance is known prior to aCROF process. It is not predetermined, if the value of the spacer heightand the inter-spacer distance is not known prior to a CROF process. Forexample, in the case that beads are sprayed on a plate as spacers, wherebeads are landed on random locations of the plate, the inter-spacerdistance is not predetermined. Another example of not predeterminedinter spacer distance is that the spacers moves during a CROF processes.

The term “a spacer is fixed on its respective plate” in a CROF processmeans that the spacer is attached to a location of a plate and theattachment to that location is maintained during a CROF (i.e. thelocation of the spacer on respective plate does not change). An exampleof “a spacer is fixed with its respective plate” is that a spacer ismonolithically made of one piece of material of the plate, and thelocation of the spacer relative to the plate surface does not changeduring CROF. An example of “a spacer is not fixed with its respectiveplate” is that a spacer is glued to a plate by an adhesive, but during ause of the plate, during CROF, the adhesive cannot hold the spacer atits original location on the plate surface and the spacer moves awayfrom its original location on the plate surface.

The term “a spacer is fixed to a plate monolithically” means the spacerand the plate behavior like a single piece of an object where, during ause, the spacer does not move or separated from its original location onthe plate.

The term “open configuration” of the two plates in a CROF process meansa configuration in which the two plates are either partially orcompletely separated apart and the spacing between the plates is notregulated by the spacers

The term “closed configuration” of the two plates in a CROF processmeans a configuration in which the plates are facing each other, thespacers and a relevant volume of the sample are between the plates, thethickness of the relevant volume of the sample is regulated by theplates and the spacers, wherein the relevant volume is at least aportion of an entire volume of the sample.

The term “a sample thickness is regulated by the plate and the spacers”in a CROF process means that for a give condition of the plates, thesample, the spacer, and the plate compressing method, the thickness ofat least a port of the sample at the closed configuration of the platescan be predetermined from the properties of the spacers and the plate.

The term “inner surface” or “sample surface” of a plate in a CROF devicerefers to the surface of the plate that touches the sample, while theother surface (that does not touch the sample) of the plate is termed“outer surface”.

The term “X-Plate” of a CROF device refers to a plate that comprisesspaces that are on the sample surface of the plate, wherein the spacershave a predetermined inter-spacer distance and spacer height, andwherein at least one of the spacers is inside the sample contact area.

The term “CROF device” refers to a device that performs a CROF process.The term “CROFed” means that a CROF process is used. For example, theterm “a sample was CROFed” means that the sample was put inside a CROFdevice, a CROF process was performed, and the sample was hold, unlessstated otherwise, at a final configuration of the CROF.

The term “CROF plates” refers to the two plates used in performing aCROF process.

The term “surface smoothness” or “surface smoothness variation” of aplanar surface refers to the average deviation of a planar surface froma perfect flat plane over a short distance that is about or smaller thana few micrometers. The surface smoothness is different from the surfaceflatness variation. A planar surface can have a good surface flatness,but poor surface smoothness.

The term “surface flatness” or “surface flatness variation” of a planarsurface refers to the average deviation of a planar surface from aperfect flat plane over a long distance that is about or larger than 10um. The surface flatness variation is different from the surfacesmoothness. A planar surface can have a good surface smoothness, butpoor surface flatness (i.e. large surface flatness variation).

The term “relative surface flatness” of a plate or a sample is the ratioof the plate surface flatness variation to the final sample thickness.

The term “final sample thickness” in a CROF process refers to, unlessspecified otherwise, the thickness of the sample at the closedconfiguration of the plates in a CORF process.

The term “compression method” in CROF refers to a method that brings twoplates from an open configuration to a closed configuration.

The term of “interested area” or “area of interest” of a plate refers tothe area of the plate that is relevant to the function that the platesperform.

The term “at most” means “equal to or less than”. For example, a spacerheight is at most 1 um, it means that the spacer height is equal to orless than 1 um.

The term “sample area” means the area of the sample in the directionapproximately parallel to the space between the plates and perpendicularto the sample thickness.

The term “sample thickness” refers to the sample dimension in thedirection normal to the surface of the plates that face each other(e.g., the direction of the spacing between the plates).

The term “plate-spacing” refers to the distance between the innersurfaces of the two plates.

The term “deviation of the final sample thickness” in a CROF means thedifference between the predetermined spacer height (determined fromfabrication of the spacer) and the average of the final samplethickness, wherein the average final sample thickness is averaged over agiven area (e.g. an average of 25 different points (4 mm apart) over 1.6cm by 1.6 cm area).

The term “uniformity of the measured final sample thickness” in a CROFprocess means the standard deviation of the measured final samplethickness over a given sample area (e.g. the standard deviation relativeto the average).

The term “relevant volume of a sample” and “relevant area of a sample”in a CROF process refers to, respectively, the volume and the area of aportion or entire volume of the sample deposited on the plates during aCROF process, that is relevant to a function to be performed by arespective method or device, wherein the function includes, but notlimited to, reduction in binding time of analyte or entity, detection ofanalytes, quantify of a volume, quantify of a concentration, mixing ofreagents, or control of a concentration (analytes, entity or reagents).

The term “some embodiments”, “in some embodiments” “in the presentinvention, in some embodiments”, “embodiment”, “one embodiment”,“another embodiment”, “certain embodiments”, “many embodiments”, oralike refers, unless specifically stated otherwise, to an embodiment(s)that is (are) applied to the entire disclosure (i.e. the entireinvention).

The term “height” or “thickness” of an object in a CROF process refersto, unless specifically stated, the dimension of the object that is inthe direction normal to a surface of the plate. For example, spacerheight is the dimension of the spacer in the direction normal to asurface of the plate, and the spacer height and the spacer thicknessmeans the same thing.

The term “area” of an object in a CROF process refers to, unlessspecifically stated, the area of the object that is parallel to asurface of the plate. For example, spacer area is the area of the spacerthat is parallel to a surface of the plate.

The term “lateral” or “laterally” in a CROF process refers to, unlessspecifically stated, the direction that is parallel to a surface of theplate.

The term “width” of a spacer in a CROF process refers to, unlessspecifically stated, a lateral dimension of the spacer.

The term “a spacer inside a sample” means that the spacer is surroundedby the sample (e.g. a pillar spacer inside a sample).

The term “critical bending span” of a plate in a CROF process refers thespan (i.e. distance) of the plate between two supports, at which thebending of the plate, for a given flexible plate, sample, andcompression force, is equal to an allowed bending. For example, if anallowed bending is 50 nm and the critical bending span is 40 um for agiven flexible plate, sample, and compression force, the bending of theplate between two neighboring spacers 40 um apart will be 50 nm, and thebending will be less than 50 nm if the two neighboring spacers is lessthan 40 um.

The term “flowable” for a sample means that when the thickness of thesample is reduced, the lateral dimension increases. For an example, astool sample is regarded flowable.

In some embodiments of the present invention, a sample under a CROFprocess do not to be flowable to benefit from the process, as long asthe sample thickness can be reduced under a CROF process. For anexample, to stain a tissue by put a dye on a surface of the CROF plate,a CROF process can reduce the tissue thickness and hence speed up thesaturation incubation time for staining by the dye.

The terms “CROF Card (or card)”, “COF Card”, “QMAX-Card”, “Q-Card”,“CROF device”, “COF device”, “QMAX-device”, “CROF plates”, “COF plates”,and “QMAX-plates” are interchangeable, except that in some embodiments,the COF card does not comprise spacers; and the terms refer to a devicethat comprises a first plate and a second plate that are movablerelative to each other into different configurations (including an openconfiguration and a closed configuration), and that comprises spacers(except some embodiments of the COF) that regulate the spacing betweenthe plates. The term “X-plate” refers to one of the two plates in a CROFcard, wherein the spacers are fixed to this plate. More descriptions ofthe COF Card, CROF Card, and X-plate are described in the provisionalapplication Ser. No. 62/456,065, filed on Feb. 7, 2017, which isincorporated herein in its entirety for all purposes.

Examples of Present Invention I. Formation of Uniform Thin Fluidic Layerby an Imprecise Force Pressing

The term “imprecise pressing force” without adding the details and thenadding a definition for imprecise pressing force.

As used herein, the term “imprecise” in the context of a force (e.g.“imprecise pressing force”) refers to a force that

(a) has a magnitude that is not precisely known or precisely predictableat the time the force is applied;

(b) has a magnitude in the range of 1N to 20N and/or a pressure in arange of 0.1 psi to 280 psi;

(c) varies in magnitude from one application of the force to the next;and

(d) the imprecision (i.e. the variation) of the force in (a) and (c) isat least 20% of the total force that actually is applied.

An imprecise force can be applied by human hand, for example, e.g., bypinching an object together between a thumb and index finger, or bypinching and rubbing an object together between a thumb and indexfinger.

A. Imprecise Force, Specify IGS{circumflex over ( )}4/hE

-   A1. A device for forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising:

a first plate, a second plate, and spacers, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates comprises an inner surface that has a        sample contact area for contacting a fluidic sample;    -   iv. each of the plates comprises, on its respective outer        surface, a force area for applying an imprecise pressing force        that forces the plates together;    -   v. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   vi. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, and a        predetermined fixed inter-spacer-distance;    -   vii. the fourth power of the inter-spacer-distance (IDS) divided        by the thickness (h) and the Young's modulus (E) of the flexible        plate (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less; and    -   viii. at least one of the spacers is inside the sample contact        area;

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample is deposited in the open configuration andthe plates are forced to the closed configuration by applying theimprecise pressing force on the force area; and in the closedconfiguration: at least part of the sample is compressed by the twoplates into a layer of highly uniform thickness and is substantiallystagnant relative to the plates, wherein the uniform thickness of thelayer is confined by the sample contact areas of the two plates and isregulated by the plates and the spacers.

-   A2. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising the steps of:    -   (a) obtaining a first plate, a second plate, and spacers,        wherein:        -   i. the plates are movable relative to each other into            different configurations;        -   ii. one or both plates are flexible;        -   iii. each of the plates comprises an inner surface that has            a sample contact area for contacting a fluidic sample;        -   iv. each of the plates comprises, on its respective outer            surface, a force area for applying an imprecise pressing            force that forces the plates together;        -   v. one or both of the plates comprise the spacers that are            permanently fixed on the inner surface of a respective            plate;        -   vi. the spacers have a predetermined substantially uniform            height that is equal to or less than 200 microns, and a            predetermined fixed inter-spacer-distance;        -   vii. the fourth power of the inter-spacer-distance (IDS)            divided by the thickness (h) and the Young's modulus (E) of            the flexible plate (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less; and        -   viii. at least one of the spacers is inside the sample            contact area;    -   (b) obtaining a fluidic sample;    -   (c) depositing the sample on one or both of the plates; when the        plates are configured in an open configuration, wherein the open        configuration is a configuration in which the two plates are        partially or completely separated apart and the spacing between        the plates is not regulated by the spacers;    -   (d) after (c), using the two plates to compress at least part of        the sample into a layer of substantially uniform thickness that        is confined by the sample contact surfaces of the plates,        wherein the uniform thickness of the layer is regulated by the        spacers and the plates, wherein the compressing comprises:        -   bringing the two plates together; and        -   conformable pressing, either in parallel or sequentially, an            area of at least one of the plates to press the plates            together to a closed configuration, wherein the conformable            pressing generates a substantially uniform pressure on the            plates over the at least part of the sample, and the            pressing spreads the at least part of the sample laterally            between the sample contact surfaces of the plates, and            wherein the closed configuration is a configuration in which            the spacing between the plates in the layer of uniform            thickness region is regulated by the spacers; and wherein            the reduced thickness of the sample reduces the time for            mixing the reagents on the storage site with the sample, and        -   wherein the force that presses the two plates into the            closed configuration is an imprecise pressing force provided            by human hand.

B. Hand Pressing, Specify Spacer Hardness-Contact Area Product

-   B1. A device for forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise force,    comprising:

a first plate, a second plate, and spacers, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates comprises, on its respective inner        surface, a sample contact area for contacting and/or compressing        a fluidic sample;    -   iv. each of the plates comprises, on its respective outer        surface, an area for applying a force that forces the plates        together;    -   v. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   vi. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, a        predetermined width, and a predetermined inter-spacer-distance;    -   vii. a ratio of the inter-spacer-distance to the spacer width is        1.5 or larger; and    -   viii. at least one of the spacers is inside the sample contact        area;

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample deposition in the open configuration; and inthe closed configuration: at least part of the sample is compressed bythe two plates into a layer of highly uniform thickness and issubstantially stagnant relative to the plates, wherein the uniformthickness of the layer is confined by the sample contact areas of thetwo plates and is regulated by the plates and the spacers; and

wherein the force that presses the two plates into the closedconfiguration is an imprecise pressing force provided by human hand.

-   B2. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising the steps of:    -   (a) obtaining a first plate, a second plate, and spacers,        wherein:        -   i. the plates are movable relative to each other into            different configurations;        -   ii. one or both plates are flexible;        -   iii. each of the plates comprises, on its respective inner            surface, a sample contact area for contacting and/or            compressing a fluidic sample;        -   iv. each of the plates comprises, on its respective outer            surface, an area for applying a force that forces the plates            together;        -   v. one or both of the plates comprise the spacers that are            permanently fixed on the inner surface of a respective            plate;        -   vi. the spacers have a predetermined substantially uniform            height that is equal to or less than 200 microns, a            predetermined width, and a predetermined            inter-spacer-distance;        -   vii. a ratio of the inter-spacer-distance to the spacer            width is 1.5 or larger; and        -   viii. at least one of the spacers is inside the sample            contact area;    -   (b) obtaining a fluidic sample;    -   (c) depositing the sample on one or both of the plates; when the        plates are configured in an open configuration, wherein the open        configuration is a configuration in which the two plates are        partially or completely separated apart and the spacing between        the plates is not regulated by the spacers;    -   (d) after (c), using the two plates to compress at least part of        the sample into a layer of substantially uniform thickness that        is confined by the sample contact surfaces of the plates,        wherein the uniform thickness of the layer is regulated by the        spacers and the plates, wherein the compressing comprises:        -   bringing the two plates together; and        -   conformable pressing, either in parallel or sequentially, an            area of at least one of the plates to press the plates            together to a closed configuration, wherein the conformable            pressing generates a substantially uniform pressure on the            plates over the at least part of the sample, and the            pressing spreads the at least part of the sample laterally            between the sample contact surfaces of the plates, and            wherein the closed configuration is a configuration in which            the spacing between the plates in the layer of uniform            thickness region is regulated by the spacers; and wherein            the reduced thickness of the sample reduces the time for            mixing the reagents on the storage site with the sample, and        -   wherein the force that presses the two plates into the            closed configuration is an imprecise pressing force provided            by human hand.            C. Hand pressing, Specify IDS/hE & Spacer Hardness-Contact            Area Product-   C1. A device for forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise force,    comprising:

a first plate, a second plate, and spacers, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates comprises, on its respective inner        surface, a sample contact area for contacting and/or compressing        a fluidic sample;    -   iv. each of the plates comprises, on its respective outer        surface, an area for applying a force that forces the plates        together;    -   v. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   vi. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, a        predetermined width, and a predetermined inter-spacer-distance;    -   vii. a ratio of the inter-spacer-distance to the spacer width is        1.5 or larger; and    -   viii. at least one of the spacers is inside the sample contact        area;

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample deposition in the open configuration; and inthe closed configuration: at least part of the sample is compressed bythe two plates into a layer of highly uniform thickness and issubstantially stagnant relative to the plates, wherein the uniformthickness of the layer is confined by the sample contact areas of thetwo plates and is regulated by the plates and the spacers;

wherein the force that presses the two plates into the closedconfiguration is imprecise, and is provided by human hand.

-   C2. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising the steps of:    -   (a) obtaining a first plate, a second plate, and spacers,        wherein:        -   i. the plates are movable relative to each other into            different configurations;        -   ii. one or both plates are flexible;        -   iii. each of the plates comprises, on its respective inner            surface, a sample contact area for contacting and/or            compressing a fluidic sample;        -   iv. each of the plates comprises, on its respective outer            surface, an area for applying a force that forces the plates            together;        -   v. one or both of the plates comprise the spacers that are            permanently fixed on the inner surface of a respective            plate;        -   vi. the spacers have a predetermined substantially uniform            height that is equal to or less than 200 microns, a            predetermined width, and a predetermined            inter-spacer-distance;        -   vii. a ratio of the inter-spacer-distance to the spacer            width is 1.5 or larger; and        -   viii. at least one of the spacers is inside the sample            contact area;    -   (b) obtaining a fluidic sample;    -   (c) depositing the sample on one or both of the plates; when the        plates are configured in an open configuration, wherein the open        configuration is a configuration in which the two plates are        partially or completely separated apart and the spacing between        the plates is not regulated by the spacers;    -   (d) after (c), using the two plates to compress at least part of        the sample into a layer of substantially uniform thickness that        is confined by the sample contact surfaces of the plates,        wherein the uniform thickness of the layer is regulated by the        spacers and the plates, wherein the compressing comprises:        -   bringing the two plates together; and        -   conformable pressing, either in parallel or sequentially, an            area of at least one of the plates to press the plates            together to a closed configuration, wherein the conformable            pressing generates a substantially uniform pressure on the            plates over the at least part of the sample, and the            pressing spreads the at least part of the sample laterally            between the sample contact surfaces of the plates, and            wherein the closed configuration is a configuration in which            the spacing between the plates in the layer of uniform            thickness region is regulated by the spacers; and wherein            the reduced thickness of the sample reduces the time for            mixing the reagents on the storage site with the sample, and        -   wherein the force that presses the two plates into the            closed configuration is an imprecise pressing force provided            by human hand.

D. Hand Pressing, Specify Pillar Spacer and Ratio of IDS/W

-   D1. A device for forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise force,    comprising:

a first plate, a second plate, and spacers, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates comprises, on its respective inner        surface, a sample contact area for contacting and/or compressing        a fluidic sample;    -   iv. each of the plates comprises, on its respective outer        surface, an area for applying a force that forces the plates        together;    -   v. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   vi. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, a        predetermined width, and a predetermined inter-spacer-distance;    -   vii. a ratio of the inter-spacer-distance to the spacer width is        1.5 or larger.    -   viii. at least one of the spacers is inside the sample contact        area; and

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample deposition in the open configuration; and inthe closed configuration: at least part of the sample is compressed bythe two plates into a layer of highly uniform thickness and issubstantially stagnant relative to the plates, wherein the uniformthickness of the layer is confined by the sample contact areas of thetwo plates and is regulated by the plates and the spacers;

wherein the force that presses the two plates into the closedconfiguration is imprecise, and is provided by human hand.

-   D2. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising the steps of:    -   (a) obtaining a first plate, a second plate, and spacers,        wherein:        -   i. the plates are movable relative to each other into            different configurations;        -   ii. one or both plates are flexible;        -   iii. each of the plates comprises, on its respective inner            surface, a sample contact area for contacting and/or            compressing a fluidic sample;        -   iv. each of the plates comprises, on its respective outer            surface, an area for applying a force that forces the plates            together;        -   v. one or both of the plates comprise the spacers that are            permanently fixed on the inner surface of a respective            plate;        -   vi. the spacers have a predetermined substantially uniform            height that is equal to or less than 200 microns, a            predetermined width, and a predetermined            inter-spacer-distance;        -   vii. a ratio of the inter-spacer-distance to the spacer            width is 1.5 or larger.        -   viii. at least one of the spacers is inside the sample            contact area; and    -   (b) obtaining a fluidic sample;    -   (c) depositing the sample on one or both of the plates; when the        plates are configured in an open configuration, wherein the open        configuration is a configuration in which the two plates are        partially or completely separated apart and the spacing between        the plates is not regulated by the spacers;    -   (d) after (c), using the two plates to compress at least part of        the sample into a layer of substantially uniform thickness that        is confined by the sample contact surfaces of the plates,        wherein the uniform thickness of the layer is regulated by the        spacers and the plates, wherein the compressing comprises:        -   bringing the two plates together; and        -   conformable pressing, either in parallel or sequentially, an            area of at least one of the plates to press the plates            together to a closed configuration, wherein the conformable            pressing generates a substantially uniform pressure on the            plates over the at least part of the sample, and the            pressing spreads the at least part of the sample laterally            between the sample contact surfaces of the plates, and            wherein the closed configuration is a configuration in which            the spacing between the plates in the layer of uniform            thickness region is regulated by the spacers; and wherein            the reduced thickness of the sample reduces the time for            mixing the reagents on the storage site with the sample, and        -   wherein the force that presses the two plates into the            closed configuration is an imprecise pressing force provided            by human hand.

E. Q (V-1) Volume Determination, Specify IGS{circumflex over ( )}4/hE

-   E1. A device for determining a relevant sample volume by pressing    with an imprecise force provided by human hand, comprising:

a first plate, a second plate, spacers, and an area-determinationdevice, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates comprises, on its respective inner        surface, a sample contact area for contacting and/or compressing        a fluidic sample that has a relevant volume to be measured;    -   iv. each of the plates comprises, on its respective outer        surface, an area for applying a force that forces the plates        together;    -   v. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   vi. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, and a        predetermined constant inter-spacer-distance;    -   vii. a fourth power of the inter-spacer-distance (IDS) divided        by the thickness (h) and the Young's modulus (E) of the flexible        plate (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.    -   viii. at least one of the spacers is inside the sample contact        area; and    -   ix. the area-determination device is configured to determine the        lateral area of the relevant volume;

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample deposition in the open configuration; and inthe closed configuration: at least part of the sample is compressed bythe two plates into a layer of highly uniform thickness and issubstantially stagnant relative to the plates, wherein the uniformthickness of the layer is confined by the sample contact areas of thetwo plates and is regulated by the plates and the spacers;

wherein the relevant volume of the sample is a partial or entire volumeof the uniform thickness layer and the value of the relevant volume isdetermined by the uniform thickness and the determined lateral area; and

wherein the force that presses the two plates into the closedconfiguration is imprecise, and is provided by human hand.

The device of any prior embodiment, wherein the area-determinationdevice is a camera.

The area-determination device comprises an area in the sample contactarea of a plate, wherein the area is less than 1/100, 1/20, 1/10, ⅙, ⅕,¼, ⅓, ½, ⅔ of the sample contact area, or in a range between any of thetwo values.

The area-determination device comprises a camera and an area in thesample contact area of a plate, wherein the area is in contact with thesample.

-   E2. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising the steps of:    -   (a) obtaining a first plate, a second plate, and spacers,        wherein:        -   i. the plates are movable relative to each other into            different configurations;        -   ii. one or both plates are flexible;        -   iii. each of the plates comprises, on its respective inner            surface, a sample contact area for contacting and/or            compressing a fluidic sample that has a relevant volume to            be measured;        -   iv. each of the plates comprises, on its respective outer            surface, an area for applying a force that forces the plates            together;        -   v. one or both of the plates comprise the spacers that are            permanently fixed on the inner surface of a respective            plate;        -   vi. the spacers have a predetermined substantially uniform            height that is equal to or less than 200 microns, and a            predetermined constant inter-spacer-distance;        -   vii. a fourth power of the inter-spacer-distance (IDS)            divided by the thickness (h) and the Young's modulus (E) of            the flexible plate (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.        -   viii. at least one of the spacers is inside the sample            contact area; and        -   ix. the area-determination device is configured to determine            the lateral area of the relevant volume;    -   (b) obtaining a fluidic sample;    -   (c) depositing the sample on one or both of the plates; when the        plates are configured in an open configuration, wherein the open        configuration is a configuration in which the two plates are        partially or completely separated apart and the spacing between        the plates is not regulated by the spacers;    -   (d) after (c), using the two plates to compress at least part of        the sample into a layer of substantially uniform thickness that        is confined by the sample contact surfaces of the plates,        wherein the uniform thickness of the layer is regulated by the        spacers and the plates, wherein the compressing comprises:        -   bringing the two plates together; and        -   conformable pressing, either in parallel or sequentially, an            area of at least one of the plates to press the plates            together to a closed configuration, wherein the conformable            pressing generates a substantially uniform pressure on the            plates over the at least part of the sample, and the            pressing spreads the at least part of the sample laterally            between the sample contact surfaces of the plates, and            wherein the closed configuration is a configuration in which            the spacing between the plates in the layer of uniform            thickness region is regulated by the spacers; and wherein            the reduced thickness of the sample reduces the time for            mixing the reagents on the storage site with the sample, and        -   wherein the force that presses the two plates into the            closed configuration is an imprecise pressing force provided            by human hand.

F. Q (V-1) Volume Determination, Specify IGS{circumflex over ( )}4/hE

-   F1. A device for determining a relevant sample volume by pressing    with an imprecise force provided by human hand, comprising:

a first plate, a second plate, spacers, and area-determination device,wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates comprises, on its respective inner        surface, a sample contact area for contacting and/or compressing        a fluidic sample that has a relevant volume to be measured;    -   iv. each of the plates comprises, on its respective outer        surface, an area for applying a force that forces the plates        together;    -   v. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   vi. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, and a        predetermined constant inter-spacer-distance;    -   vii. a fourth power of the inter-spacer-distance (IDS) divided        by the thickness (h) and the Young's modulus (E) of the flexible        plate (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.    -   viii. at least one of the spacers is inside the sample contact        area; and    -   ix. the area-determination device is configured to determine the        lateral area of the relevant volume;

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample deposition in the open configuration; and inthe closed configuration: at least part of the sample is compressed bythe two plates into a layer of highly uniform thickness and issubstantially stagnant relative to the plates, wherein the uniformthickness of the layer is confined by the sample contact areas of thetwo plates and is regulated by the plates and the spacers;

wherein the relevant volume of the sample is a partial or entire volumeof the uniform thickness layer and the value of the relevant volume isdetermined by the uniform thickness and the determined lateral area; and

wherein the force that presses the two plates into the closedconfiguration is imprecise, and is provided by human hand.

-   F2. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising the steps of:    -   (a) obtaining a first plate, a second plate, and spacers,        wherein:        -   i. the plates are movable relative to each other into            different configurations;        -   ii. one or both plates are flexible;        -   iii. each of the plates comprises, on its respective inner            surface, a sample contact area for contacting and/or            compressing a fluidic sample that has a relevant volume to            be measured;        -   iv. each of the plates comprises, on its respective outer            surface, an area for applying a force that forces the plates            together;        -   v. one or both of the plates comprise the spacers that are            permanently fixed on the inner surface of a respective            plate;        -   vi. the spacers have a predetermined substantially uniform            height that is equal to or less than 200 microns, and a            predetermined constant inter-spacer-distance;        -   vii. a fourth power of the inter-spacer-distance (IDS)            divided by the thickness (h) and the Young's modulus (E) of            the flexible plate (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.        -   viii. at least one of the spacers is inside the sample            contact area; and        -   ix. the area-determination device is configured to determine            the lateral area of the relevant volume;    -   (b) obtaining a fluidic sample;    -   (c) depositing the sample on one or both of the plates; when the        plates are configured in an open configuration, wherein the open        configuration is a configuration in which the two plates are        partially or completely separated apart and the spacing between        the plates is not regulated by the spacers;    -   (d) after (c), using the two plates to compress at least part of        the sample into a layer of substantially uniform thickness that        is confined by the sample contact surfaces of the plates,        wherein the uniform thickness of the layer is regulated by the        spacers and the plates, wherein the compressing comprises:        -   bringing the two plates together; and        -   conformable pressing, either in parallel or sequentially, an            area of at least one of the plates to press the plates            together to a closed configuration, wherein the conformable            pressing generates a substantially uniform pressure on the            plates over the at least part of the sample, and the            pressing spreads the at least part of the sample laterally            between the sample contact surfaces of the plates, and            wherein the closed configuration is a configuration in which            the spacing between the plates in the layer of uniform            thickness region is regulated by the spacers; and wherein            the reduced thickness of the sample reduces the time for            mixing the reagents on the storage site with the sample, and        -   wherein the force that presses the two plates into the            closed configuration is an imprecise pressing force provided            by human hand.    -   1. The device or method of any prior embodiment, wherein spacers        have a flat top.    -   2. The device or method of any prior embodiment, wherein the        device is further configured to have, after the pressing force        is removed, a sample thickness that is substantially the same in        thickness and uniformity as that when the force is applied.    -   3. The device or method of any prior embodiment, wherein the        imprecise force is provided by human hand.    -   4. The device or method of any prior embodiment, wherein the        inter spacer distance is substantially constant.    -   5. The device or method of any prior embodiment, wherein the        inter spacer distance is substantially periodic in the area of        the uniform sample thickness area.    -   6. The device or method of any prior embodiment, wherein the        multiplication product of the filling factor and the Young's        modulus of the spacer is 2 MPa or larger.    -   The device or method of any prior embodiment, wherein the force        is applied by hand directly or indirectly.    -   8. The device or method of any prior embodiment, wherein the        force applied is in the range of 5 N to 20 N.    -   9. The device or method of any prior embodiment wherein the        highly uniform layer has a thickness that varies by less than        15%, 10%, or 5% of an average thickness.    -   10. The device or method of any prior embodiment, wherein the        imprecise force is applied by pinching the device between a        thumb and forefinger.    -   11. The device or method of any prior embodiment, wherein the        predetermined sample thickness is larger than the spacer height.    -   12. The device or method of any prior embodiment, wherein the        device holds itself in the closed configuration after the        pressing force has been removed.    -   13. The device or method of any prior embodiment, wherein the        uniform thickness sample layer area is larger than that area        upon which the pressing force is applied.    -   14. The device or method of any prior embodiment, wherein the        spacers do not significantly deform during application of the        pressing force.    -   15. The device or method of any prior embodiment, wherein the        pressing force is not predetermined beforehand and is not        measured.    -   16. The device of any prior device embodiment, wherein the        analyte comprises a molecule (e.g., a protein, peptides, DNA,        RNA, nucleic acid, or other molecule), cells, tissues, viruses,        and nanoparticles with different shapes.    -   17. The device of any prior device embodiment, wherein the        analyte comprises white blood cells, red blood cells and        platelets.    -   18. The device of any prior device embodiment, wherein the        analyte is stained.    -   19. The method or device of any prior embodiment, wherein the        inter spacer distance (SD) is equal or less than about 120 um        (micrometer).    -   20. The method or device of any prior embodiment, wherein the        inter spacer distance (SD) is equal or less than about 100 um        (micrometer).    -   21. The method or device of any prior embodiment, wherein the        fourth power of the inter-spacer-distance (ISD) divided by the        thickness (h) and the Young's modulus (E) of the flexible plate        (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.    -   22. The method or device of any prior embodiment, wherein the        fourth power of the inter-spacer-distance (ISD) divided by the        thickness (h) and the Young's modulus (E) of the flexible plate        (ISD⁴/(hE)) is 5×10⁵ um³/GPa or less.    -   23. The method or device of any prior embodiment, wherein the        spacers have pillar shape, a substantially flat top surface, a        predetermined substantially uniform height, and a predetermined        constant inter-spacer distance that is at least about 2 times        larger than the size of the analyte, wherein the Young's modulus        of the spacers times the filling factor of the spacers is equal        or larger than 2 MPa, wherein the filling factor is the ratio of        the spacer contact area to the total plate area, and wherein,        for each spacer, the ratio of the lateral dimension of the        spacer to its height is at least 1 (one).    -   24. The method or device of any prior embodiment, wherein the        spacers have pillar shape, a substantially flat top surface, a        predetermined substantially uniform height, and a predetermined        constant inter-spacer distance that is at least about 2 times        larger than the size of the analyte, wherein the Young's modulus        of the spacers times the filling factor of the spacers is equal        or larger than 2 MPa, wherein the filling factor is the ratio of        the spacer contact area to the total plate area, and wherein,        for each spacer, the ratio of the lateral dimension of the        spacer to its height is at least 1 (one), wherein the fourth        power of the inter-spacer-distance (ISD) divided by the        thickness (h) and the Young's modulus (E) of the flexible plate        (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.    -   25. The device of any prior device embodiment, wherein the ratio        of the inter-spacing distance of the spacers to the average        width of the spacer is 2 or larger, and the filling factor of        the spacers multiplied by the Young's modulus of the spacers is        2 MPa or larger.    -   26. The method or device of any prior embodiment, wherein the        analytes is the analyte in 5 detection of proteins, peptides,        nucleic acids, synthetic compounds, and inorganic compounds.    -   27. The method or device of any prior embodiment, wherein the        sample is a biological sample selected from amniotic fluid,        aqueous humour, vitreous humour, blood (e.g., whole blood,        fractionated blood, plasma or serum), breast milk, cerebrospinal        fluid (CSF), cerumen (earwax), chyle, chime, endolymph,        perilymph, feces, breath, gastric acid, gastric juice, lymph,        mucus (including nasal drainage and phlegm), pericardial fluid,        peritoneal fluid, pleural fluid, pus, rheum, saliva, exhaled        breath condensates, sebum, semen, sputum, sweat, synovial fluid,        tears, vomit, and urine.    -   28. The method or device of any prior embodiment, wherein the        spacers have a shape of pillars and a ratio of the width to the        height of the pillar is equal or larger than one.    -   29. The method of any prior embodiment, wherein the sample that        is deposited on one or both of the plates has an unknown volume.    -   30. The method or device of any prior embodiment, wherein the        samples is for the detection, purification and quantification of        chemical compounds or biomolecules that correlates with the        stage of certain diseases.    -   31. The method or device of any prior embodiment, wherein the        samples is related to infectious and parasitic disease,        injuries, cardiovascular disease, cancer, mental disorders,        neuropsychiatric disorders, pulmonary diseases, renal diseases,        and other and organic diseases.    -   32. The method or device of any prior embodiment, wherein the        samples is related to the detection, purification and        quantification of microorganism.    -   33. The method or device of any prior embodiment, wherein the        samples is related to virus, fungus and bacteria from        environment, e.g., water, soil, or biological samples.    -   34. The method or device of any prior embodiment, wherein the        samples is related to the detection, quantification of chemical        compounds or biological samples that pose hazard to food safety        or national security, e.g. toxic waste, anthrax.    -   35. The method or device of any prior embodiment, wherein the        samples is related to quantification of vital parameters in        medical or physiological monitor.    -   36. The method or device of any prior embodiment, wherein the        samples is related to glucose, blood, oxygen level, total blood        count.    -   37. The method or device of any prior embodiment, wherein the        samples is related to the detection and quantification of        specific DNA or RNA from biosamples.    -   38. The method or device of any prior embodiment, wherein the        samples is related to the sequencing and comparing of genetic        sequences in DNA in the chromosomes and mitochondria for genome        analysis.    -   39. The method or device of any prior embodiment, wherein the        samples is related to detect reaction products, e.g., during        synthesis or purification of pharmaceuticals.    -   40. The method or device of any prior embodiment, wherein the        samples is cells, tissues, bodily fluids, and stool.    -   41. The method or device of any prior embodiment, wherein the        sample is the sample in the detection of proteins, peptides,        nucleic acids, synthetic compounds, inorganic compounds.    -   42. The method or device of any prior embodiment, wherein the        sample is the sample in the fields of human, veterinary,        agriculture, foods, environments, and drug testing.    -   43. The method or device of any prior embodiment, wherein the        sample is a biological sample is selected from blood, serum,        plasma, a nasal swab, a nasopharyngeal wash, saliva, urine,        gastric fluid, spinal fluid, tears, stool, mucus, sweat, earwax,        oil, a glandular secretion, cerebral spinal fluid, tissue,        semen, vaginal fluid, interstitial fluids derived from tumorous        tissue, ocular fluids, spinal fluid, a throat swab, breath,        hair, finger nails, skin, biopsy, placental fluid, amniotic        fluid, cord blood, lymphatic fluids, cavity fluids, sputum, pus,        microbiota, meconium, breast milk, exhaled condensate        nasopharyngeal wash, throat swab, stool samples, hair, finger        nail, ear wax, breath, connective tissue, muscle tissue, nervous        tissue, epithelial tissue, cartilage, cancerous sample, or bone.    -   44. The devices or methods of any prior embodiment, wherein the        spacers regulating the layer of uniform thickness have a filling        factor of at least 1%, wherein the filling factor is the ratio        of the spacer area in contact with the layer of uniform        thickness to the total plate area in contact with the layer of        uniform thickness.

Flat Top of Pillar Spacers

In certain embodiments of the present invention, the spacers are pillarsthat have a flat top and a foot fixed on one plate, wherein the flat tophas a smoothness with a small surface variation, and the variation isless than 5, 10 nm, 20 nm, 30 nm, 50 nm, 100 nm, 200 nm, 300 nm, 400 nm,500 nm, 600 nm, 700 nm, 800 nm, 1000 nm, or in a range between any twoof the values. A preferred flat pillar top smoothness is that surfacevariation of 50 nm or less.

Furthermore, the surface variation is relative to the spacer height andthe ratio of the pillar flat top surface variation to the spacer heightis less than 0.5%, 1%, 3%, 5%, 7%, 10%, 15%, 20%, 30%, 40%, or in arange between any two of the values. A preferred flat pillar topsmoothness has a ratio of the pillar flat top surface variation to thespacer height is less than 2%, 5%, or 10%.

Sidewall Angle of Pillar Spacers

In certain embodiments of the present invention, the spacers are pillarsthat have a sidewall angle. In some embodiments, the sidewall angle isless than 5 degree (measured from the normal of a surface), 10 degree,20 degree, 30 degree, 40 degree, 50 degree, 70 degree, or in a rangebetween any two of the values. In a preferred embodiment, the sidewallangle is less 5 degree, 10 degree, or 20 degree.

Formation of Uniform Thin Fluidic Layer by an Imprecise Force Pressing

In certain embodiment of the present invention, a uniform thin fluidicsample layer is formed by using a pressing with an imprecise force. Theterm “imprecise pressing force” without adding the details and thenadding a definition for imprecise pressing force. As used herein, theterm “imprecise” in the context of a force (e.g. “imprecise pressingforce”) refers to a force that

(a) has a magnitude that is not precisely known or precisely predictableat the time the force is applied; (b) has a pressure in the range of0.01 kg/cm² (centimeter square) to 100 kg/cm², (c) varies in magnitudefrom one application of the force to the next; and (d) the imprecision(i.e. the variation) of the force in (a) and (c) is at least 20% of thetotal force that actually is applied.

An imprecise force can be applied by human hand, for example, e.g., bypinching an object together between a thumb and index finger, or bypinching and rubbing an object together between a thumb and indexfinger.

In some embodiments, the imprecise force by the hand pressing has apressure of 0.01 kg/cm2, 0.1 kg/cm2, 0.5 kg/cm2, 1 kg/cm2, 2 kg/cm2,kg/cm2, 5 kg/cm2, 10 kg/cm2, 20 kg/cm2, 30 kg/cm2, 40 kg/cm2, 50 kg/cm2,60 kg/cm2, 100 kg/cm2, 150 kg/cm2, 200 kg/cm2, or a range between anytwo of the values; and a preferred range of 0.1 kg/cm2 to 0.5 kg/cm2,0.5 kg/cm2 to 1 kg/cm2, 1 kg/cm2 to 5 kg/cm2, 5 kg/cm2 to 10 kg/cm2(Pressure).

Spacer Filling Factor.

The term “spacer filling factor” or “filling factor” refers to the ratioof the spacer contact area to the total plate area”, wherein the spacercontact area refers, at a closed configuration, the contact area thatthe spacer's top surface contacts to the inner surface of a plate, andthe total plate area refers the total area of the inner surface of theplate that the flat top of the spacers contact. Since there are twoplates and each spacer has two contact surfaces each contacting oneplate, the filling fact is the filling factor of the smallest.

For example, if the spacers are pillars with a flat top of a squareshape (10 um×10 um), a nearly uniform cross-section and 2 um tall, andthe spacers are periodic with a period of 100 um, then the filing factorof the spacer is 1%. If in the above example, the foot of the pillarspacer is a square shape of 15 um×15 um, then the filling factor isstill 1% by the definition.

IDS{circumflex over ( )}4/hE

-   A1. A device for forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing, comprising:

a first plate, a second plate, and spacers, wherein:

-   -   ix. the plates are movable relative to each other into different        configurations;    -   x. one or both plates are flexible;    -   xi. each of the plates comprises an inner surface that has a        sample contact area for contacting a fluidic sample;    -   xii. each of the plates comprises, on its respective outer        surface, a force area for applying an pressing force that forces        the plates together;    -   xiii. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   xiv. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, and a        predetermined fixed inter-spacer-distance;    -   xv. the fourth power of the inter-spacer-distance (ISD) divided        by the thickness (h) and the Young's modulus (E) of the flexible        plate (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less; and    -   xvi. at least one of the spacers is inside the sample contact        area;

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample is deposited in the open configuration andthe plates are forced to the closed configuration by applying thepressing force on the force area; and in the closed configuration: atleast part of the sample is compressed by the two plates into a layer ofhighly uniform thickness and is substantially stagnant relative to theplates, wherein the uniform thickness of the layer is confined by thesample contact areas of the two plates and is regulated by the platesand the spacers.

-   A2. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing, comprising the steps of:    -   (e) obtaining a device of embodiment A1;    -   (f) depositing a fluidic sample on one or both of the plates;        when the plates are configured in an open configuration, wherein        the open configuration is a configuration in which the two        plates are partially or completely separated apart and the        spacing between the plates is not regulated by the spacers;    -   (g) after (b), forcing the two plates into a closed        configuration, in which: at least part of the sample is        compressed by the two plates into a layer of substantially        uniform thickness, wherein the uniform thickness of the layer is        confined by the sample contact surfaces of the plates and is        regulated by the plates and the spacers.-   A3. A device for analyzing a fluidic sample, comprising:

a first plate, a second plate, and spacers, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates has, on its respective inner surface, a        sample contact area for contacting a fluidic sample,    -   iv. one or both of the plates comprise the spacers and the        spacers are fixed on the inner surface of a respective plate;    -   v. the spacers have a predetermined substantially uniform height        that is equal to or less than 200 microns, and the        inter-spacer-distance is predetermined;    -   vi. the Young's modulus of the spacers multiplied by the filling        factor of the spacers is at least 2 MPa; and    -   vii. at least one of the spacers is inside the sample contact        area; and

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates; and

wherein another of the configurations is a closed configuration which isconfigured after the sample is deposited in the open configuration; andin the closed configuration: at least part of the sample is compressedby the two plates into a layer of highly uniform thickness, wherein theuniform thickness of the layer is confined by the sample contactsurfaces of the plates and is regulated by the plates and the spacers.

-   A4. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing, comprising the steps of:    -   (a) obtaining a device of embodiment A3;    -   (b) depositing a fluidic sample on one or both of the plates;        when the plates are configured in an open configuration, wherein        the open configuration is a configuration in which the two        plates are partially or completely separated apart and the        spacing between the plates is not regulated by the spacers;    -   (c) after (b), forcing the two plates into a closed        configuration, in which: at least part of the sample is        compressed by the two plates into a layer of substantially        uniform thickness, wherein the uniform thickness of the layer is        confined by the sample contact surfaces of the plates and is        regulated by the plates and the spacers.-   A5. A device for analyzing a fluidic sample, comprising:

a first plate and a second plate, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates has, on its respective surface, a sample        contact area for contacting a sample that contains an analyte,    -   iv. one or both of the plates comprise spacers that are        permanently fixed to a plate within a sample contact area,        wherein the spacers have a predetermined substantially uniform        height and a predetermined fixed inter-spacer distance that is        at least about 2 times larger than the size of the analyte, up        to 200 urn, and wherein at least one of the spacers is inside        the sample contact area;

wherein one of the configurations is an open configuration, in which:the two plates are separated apart, the spacing between the plates isnot regulated by the spacers, and the sample is deposited on one or bothof the plates; and

wherein another of the configurations is a closed configuration which isconfigured after the sample deposition in the open configuration; and inthe closed configuration: at least part of the sample is compressed bythe two plates into a layer of highly uniform thickness, wherein theuniform thickness of the layer is confined by the sample contactsurfaces of the plates and is regulated by the plates and the spacers.

-   A6. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing, comprising the steps of:    -   (a) obtaining a device of embodiment A5;    -   (b) depositing a fluidic sample on one or both of the plates;        when the plates are configured in an open configuration, wherein        the open configuration is a configuration in which the two        plates are partially or completely separated apart and the        spacing between the plates is not regulated by the spacers;    -   (c) after (b), forcing the two plates into a closed        configuration, in which: at least part of the sample is        compressed by the two plates into a layer of substantially        uniform thickness, wherein the uniform thickness of the layer is        confined by the sample contact surfaces of the plates and is        regulated by the plates and the spacers.-   A7. A device for forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing, comprising:

a first plate, a second plate, and spacers, wherein:

-   -   ix. the plates are movable relative to each other into different        configurations;    -   x. one or both plates are flexible;    -   xi. each of the plates comprises, on its respective inner        surface, a sample contact area for contacting and/or compressing        a fluidic sample;    -   xii. each of the plates comprises, on its respective outer        surface, an area for applying a force that forces the plates        together;    -   xiii. one or both of the plates comprise the spacers that are        permanently fixed on the inner surface of a respective plate;    -   xiv. the spacers have a predetermined substantially uniform        height that is equal to or less than 200 microns, a        predetermined width, and a predetermined fixed        inter-spacer-distance;    -   xv. a ratio of the inter-spacer-distance to the spacer width is        1.5 or larger; and    -   xvi. at least one of the spacers is inside the sample contact        area;

wherein one of the configurations is an open configuration, in which:the two plates are partially or completely separated apart, the spacingbetween the plates is not regulated by the spacers, and the sample isdeposited on one or both of the plates;

wherein another of the configurations is a closed configuration which isconfigured after the sample deposition in the open configuration; and inthe closed configuration: at least part of the sample is compressed bythe two plates into a layer of highly uniform thickness and issubstantially stagnant relative to the plates, wherein the uniformthickness of the layer is confined by the sample contact areas of thetwo plates and is regulated by the plates and the spacers.

-   A8. A method of forming a thin fluidic sample layer with a uniform    predetermined thickness by pressing with an imprecise pressing    force, comprising the steps of:    -   (a) obtaining a device of embodiment A7;    -   (b) obtaining a fluidic sample;    -   (e) depositing the sample on one or both of the plates; when the        plates are configured in an open configuration, wherein the open        configuration is a configuration in which the two plates are        partially or completely separated apart and the spacing between        the plates is not regulated by the spacers;    -   (d) after (c), forcing the two plates into a closed        configuration, in which: at least part of the sample is        compressed by the two plates into a layer of substantially        uniform thickness, wherein the uniform thickness of the layer is        confined by the sample contact surfaces of the plates and is        regulated by the plates and the spacers.

The devices or methods of any prior embodiment, wherein the spacers havea shape of pillar with a foot fixed on one of the plate and a flat topsurface for contacting the other plate.

The devices or methods of any prior embodiment, wherein the spacers havea shape of pillar with a foot fixed on one of the plate, a flat topsurface for contacting the other plate, substantially uniformcross-section.

The devices or methods of any prior embodiment, wherein the spacers havea shape of pillar with a foot fixed on one of the plate and a flat topsurface for contacting the other plate, wherein the flat top surface ofthe pillars has a variation in less than 10 nm.

The devices or methods of any prior embodiment, wherein the spacers havea shape of pillar with a foot fixed on one of the plate and a flat topsurface for contacting the other plate, wherein the flat top surface ofthe pillars has a variation in less than 50 nm.

The devices or methods of any prior embodiment, wherein the spacers havea shape of pillar with a foot fixed on one of the plate and a flat topsurface for contacting the other plate, wherein the flat top surface ofthe pillars has a variation in less than 50 nm.

The devices or methods of any prior embodiment, wherein the spacers havea shape of pillar with a foot fixed on one of the plate and a flat topsurface for contacting the other plate, wherein the flat top surface ofthe pillars has a variation in less than 10 nm, 20 nm, 30 nm, 100 nm,200 nm, or in a range of any two of the values.

The devices or methods of any prior embodiment, wherein the Young'smodulus of the spacers multiplied by the filling factor of the spacersis at least 2 MPa.

The devices or methods of any prior embodiment, wherein the samplecomprises an analyte and the predetermined constant inter-spacerdistance is at least about 2 times larger than the size of the analyte,up to 200 um.

The devices or methods of any prior embodiment, wherein the samplecomprise an analyte, the predetermined constant inter-spacer distance isat least about 2 times larger than the size of the analyte, up to 200um, and the Young's modulus of the spacers multiplied by the fillingfactor of the spacers is at least 2 MPa.

The devices or methods of any prior embodiment, wherein a fourth powerof the inter-spacer-distance (IDS) divided by the thickness (h) and theYoung's modulus (E) of the flexible plate (ISD{circumflex over( )}4/(hE)) is 5×10{circumflex over ( )}6 um{circumflex over ( )}3/GPaor less.

The devices or methods of any prior embodiment, wherein a fourth powerof the inter-spacer-distance (IDS) divided by the thickness (h) and theYoung's modulus (E) of the flexible plate (ISD{circumflex over( )}4/(hE)) is 1×10{circumflex over ( )}6 um{circumflex over ( )}3/GPaor less.

The devices or methods of any prior embodiment, wherein a fourth powerof the inter-spacer-distance (IDS) divided by the thickness (h) and theYoung's modulus (E) of the flexible plate (ISD{circumflex over( )}4/(hE)) is 5×10{circumflex over ( )}5 um{circumflex over ( )}3/GPaor less.

The devices or methods of any prior embodiment, wherein the Young'smodulus of the spacers multiplied by the filling factor of the spacersis at least 2 MPa, and a fourth power of the inter-spacer-distance (IDS)divided by the thickness (h) and the Young's modulus (E) of the flexibleplate (ISD{circumflex over ( )}4/(hE)) is 1×10{circumflex over ( )}5um{circumflex over ( )}3/GPa or less.

The devices or methods of any prior embodiment, wherein the Young'smodulus of the spacers multiplied by the filling factor of the spacersis at least 2 MPa, and a fourth power of the inter-spacer-distance (IDS)divided by the thickness (h) and the Young's modulus (E) of the flexibleplate (ISD{circumflex over ( )}4/(hE)) is 1×10{circumflex over ( )}4um″3/GPa or less.

The methods of any prior embodiment, wherein the pressing force is animprecise force that has a magnitude which is, at the time that theforce is applied, either (a) unknown and unpredictable, or (b) cannot beknown and cannot be predicted within an accuracy equal or better than20% of the average pressing force applied.

The methods of any prior embodiment, wherein the pressing force is animprecise force that has a magnitude which is, at the time that theforce is applied, either (a) unknown and unpredictable, or (b) cannot beknown and cannot be predicted within an accuracy equal or better than30% of the average pressing force applied.

The methods of any prior embodiment, wherein the pressing force is animprecise force that has a magnitude which is, at the time that theforce is applied, either (a) unknown and unpredictable, or (b) cannot beknown and cannot be predicted within an accuracy equal or better than30% of the average pressing force applied; and wherein the layer ofhighly uniform thickness has a variation in thickness uniform of 20% orless.

The methods of any prior embodiment, wherein the pressing force is animprecise force that has a magnitude which cannot, at the time that theforce is applied, be determined within an accuracy equal or better than30%, 40%, 50%, 70%, 100%, 200%, 300%, 500%, 1000%, 2000%, or in a rangebetween any of the two values.

The devices or methods of any prior embodiment, wherein the flexibleplate has a thickness of in the range of 10 um to 200 um.

The devices or methods of any prior embodiment, wherein the flexibleplate has a thickness of in the range of 20 um to 100 um.

The devices or methods of any prior embodiment, wherein the flexibleplate has a thickness of in the range of 25 um to 180 um.

The devices or methods of any prior embodiment, wherein the flexibleplate has a thickness of in the range of 200 um to 260 um.

The devices or methods of any prior embodiment, wherein the flexibleplate has a thickness of equal to or less than 250 um, 225 um, 200 um,175 um, 150 um, 125 um, 100 um, 75 um, 50 um, 25 um, 10 um, 5 um, 1 um,or in a range between the two of the values.

The devices or methods of any prior method, wherein the sample has aviscosity in the range of 0.1 to 4 (mPa s).

The devices or methods of any prior embodiment, wherein the flexibleplate has a thickness of in the range of 200 um to 260 um.

The devices or methods of any prior embodiment, wherein the flexibleplate has a thickness in the range of 20 um to 200 um and Young'smodulus in the range 0.1 to 5 GPa.

-   -   45. The method of any prior claim, wherein the sample deposition        of step (b) is a deposition directly from a subject to the plate        without using any transferring devices.    -   46. The method any prior claim, wherein during the deposition of        step (b), the amount of the sample deposited on the plate is        unknown.    -   47. The method of any prior claim, wherein the method further        comprises an analyzing step (e) that analyze the sample.    -   48. The method of any prior claim, wherein the analyzing        step (e) comprises calculating the volume of a relevant sample        volume by measuring the lateral area of the relevant sample        volume and calculating the volume from the lateral area and the        predetermined spacer height.    -   49. The method of any prior claim, wherein the analyzing        step (e) comprises measuring:        -   i. imaging, illuminescence selected from photoluminescence,            electroluminescence, and electrochemiluminescence,        -   iii. surface Raman scattering,        -   iv. electrical impedance selected from resistance,            capacitance, and inductance, or        -   v. any combination of i-iv.    -   50. The method of any prior claim, wherein the analyzing        step (e) comprises reading, image analysis, or counting of the        analyte, or a combination of thereof.    -   51. The method of any prior claim, wherein the sample contains        one or plurality of analytes, and one or both plate sample        contact surfaces comprise one or a plurality of binding sites        that each binds and immobilize a respective analyte.    -   52. The method of any prior claim, wherein one or both plate        sample contact surfaces comprise one or a plurality of storage        sites that each stores a reagent or reagents, wherein the        reagent(s) dissolve and diffuse in the sample during or after        step (c).    -   53. The method of any prior claim, wherein one or both plate        sample contact surfaces comprises one or a plurality of        amplification sites that are each capable of amplifying a signal        from the analyte or a label of the analyte when the analyte or        label is within 500 nm from an amplification site.    -   54. The method of any prior claim, wherein:        -   i. one or both plate sample contact surfaces comprise one or            a plurality of binding sites that each binds and immobilize            a respective analyte; or        -   ii. one or both plate sample contact surfaces comprise, one            or a plurality of storage sites that each stores a reagent            or reagents; wherein the reagent(s) dissolve and diffuse in            the sample during or after step (c), and wherein the sample            contains one or plurality of analytes; or        -   iii. one or a plurality of amplification sites that are each            capable of amplifying a signal from the analyte or a label            of the analyte when the analyte or label is 500 nm from the            amplification site; or        -   iv. any combination of i to iii.    -   55. The devices or methods of any prior embodiment, wherein the        liquid sample is a biological sample selected from amniotic        fluid, aqueous humour, vitreous humour, blood (e.g., whole        blood, fractionated blood, plasma or serum), breast milk,        cerebrospinal fluid (CSF), cerumen (earwax), chyle, chime,        endolymph, perilymph, feces, breath, gastric acid, gastric        juice, lymph, mucus (including nasal drainage and phlegm),        pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum,        saliva, exhaled breath condensates, sebum, semen, sputum, sweat,        synovial fluid, tears, vomit, and urine.    -   56. The devices or methods of any prior embodiment, wherein the        layer of uniform thickness in the closed configuration is less        than 150 um.    -   57. The method of any prior claim, wherein the pressing is        provided by a pressured liquid, a pressed gas, or a conformal        material.    -   58. The method of any prior claim, wherein the analyzing        comprises counting cells in the layer of uniform thickness.    -   59. The method of any prior claim, wherein the analyzing        comprises performing an assay in the layer of uniform thickness.    -   60. The devices or methods of any prior embodiment, wherein the        assay is a binding assay or biochemical assay.    -   61. The method of any prior claim, wherein the sample deposited        has a total volume less 0.5 uL    -   62. The method of any prior claim, wherein multiple drops of        sample are deposited onto one or both of the plates.    -   63. The devices or methods of any prior embodiment, wherein the        inter-spacer distance is in the range of 1 □m to 120 □m.    -   64. The devices or methods of any prior embodiment, wherein the        inter-spacer distance is in the range of 120 □m to 50 □m.    -   65. The devices or methods of any prior embodiment, wherein the        inter-spacer distance is in the range of 120 □m to 200 □m.    -   66. The device of any prior device claim, wherein the flexible        plates have a thickness in the range of 20 um to 250 um and        Young's modulus in the range 0.1 to 5 GPa.    -   67. The device of any prior device claim, wherein for a flexible        plate, the thickness of the flexible plate times the Young's        modulus of the flexible plate is in the range 60 to 750 GPa-um.    -   68. The device of any prior device claim, wherein the layer of        uniform thickness sample is uniform over a lateral area that is        at least 1 mm².    -   69. The device of any prior device claim, wherein the layer of        uniform thickness sample is uniform over a lateral area that is        at least 3 mm².    -   70. The device of any prior device claim, wherein the layer of        uniform thickness sample is uniform over a lateral area that is        at least 5 mm².    -   71. The device of any prior device claim, wherein the layer of        uniform thickness sample is uniform over a lateral area that is        at least 10 mm².    -   72. The device of any prior device claim, wherein the layer of        uniform thickness sample is uniform over a lateral area that is        at least 20 mm².    -   73. The device of any prior device claim, wherein the layer of        uniform thickness sample is uniform over a lateral area that is        in a range of 20 mm² to 100 mm².    -   74. The device of any prior device claim, wherein the layer of        uniform thickness sample has a thickness uniformity of up to        +/−5% or better.    -   75. The device of any prior device claim, wherein the layer of        uniform thickness sample has a thickness uniformity of up to        +1-10% or better.    -   76. The device of any prior device claim, wherein the layer of        uniform thickness sample has a thickness uniformity of up to        +/−20% or better.    -   77. The device of any prior device claim, wherein the layer of        uniform thickness sample has a thickness uniformity of up to        +/−30% or better.    -   78. The device of any prior device claim, wherein the layer of        uniform thickness sample has a thickness uniformity of up to        +/−40% or better.    -   79. The device of any prior device claim, wherein the layer of        uniform thickness sample has a thickness uniformity of up to        +/−50% or better.    -   80. The device of any prior device claim, wherein the spacers        are pillars with a cross-sectional shape selected from round,        polygonal, circular, square, rectangular, oval, elliptical, or        any combination of the same.    -   81. The device of any prior device claim, wherein the spacers        have pillar shape, have a substantially flat top surface, and        have substantially uniform cross-section, wherein, for each        spacer, the ratio of the lateral dimension of the spacer to its        height is at least 1.    -   82. The device of any prior device claim, wherein the inter        spacer distance is periodic.    -   83. The device of any prior device claim, wherein the spacers        have a filling factor of 1% or higher, wherein the filling        factor is the ratio of the spacer contact area to the total        plate area.    -   84. The device of any prior device claim, wherein the Young's        modulus of the spacers times the filling factor of the spacers        is equal or larger than 20 MPa, wherein the filling factor is        the ratio of the spacer contact area to the total plate area.    -   85. The device of any prior device claim, wherein the spacing        between the two plates at the closed configuration is in less        200 um.    -   86. The device of any prior device claim, wherein the spacing        between the two plates at the closed configuration is a value        selected from between 1.8 um and 3.5 um.    -   87. The device of any prior device claim, wherein the spacing        are fixed on a plate by directly embossing the plate or        injection molding of the plate.    -   88. The device of any prior device claim, wherein the materials        of the plate and the spacers are selected from polystyrene,        PMMA, PC, COC, COP, or another plastic.    -   89. The device of any prior device claim, wherein the spacers        have a pillar shape, and the sidewall corners of the spacers        have a round shape with a radius of curvature at least 1 □M.    -   90. The device of any prior device claim, wherein the spacers        have a density of at least 1000/mm².    -   91. The device of any prior device claim, wherein at least one        of the plates is transparent.    -   92. The device of any prior device claim, wherein the mold used        to make the spacers is fabricated by a mold containing features        that are fabricated by either (a) directly reactive ion etching        or ion beam etched or (b) by a duplication or multiple        duplication of the features that are reactive ion etched or ion        beam etched.    -   93. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor is in the        range of 1% to 5%.

The devices or methods of any prior embodiment, wherein the surfacevariation is relative to the spacer height and the ratio of the pillarflat top surface variation to the spacer height is less than 0.5%, 1%,3%, 5%, 7%, 10%, 15%, 20%, 30%, 40%, or in a range between any two ofthe values. A preferred flat pillar top smoothness has a ratio of thepillar flat top surface variation to the spacer height is less than 2%,5%, or 10%.

-   -   94. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor is in the        range of 1% to 5%.    -   95. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor is in the        range of 5% to 10%.    -   96. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor is in the        range of 10% to 20%.    -   97. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor is in the        range of 20% to 30%.    -   98. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor is 5%, 10%,        20%, 30%, 40%, 50%, or in a range of any two of the values.    -   99. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor is 50%,        60%, 70%, 80%, or in a range of any two of the values.    -   100. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor multiplies        the Young's modulus of the spacer is in the range of 2 MPa and        10 MPa.    -   101. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor multiplies        the Young's modulus of the spacer is in the range of 10 MPa and        20 MPa.    -   102. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor multiplies        the Young's modulus of the spacer is in the range of 20 MPa and        40 MPa.    -   103. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor multiplies        the Young's modulus of the spacer is in the range of 40 MPa and        80 MPa.    -   104. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor multiplies        the Young's modulus of the spacer is in the range of 80 MPa and        120 MPa.    -   105. The devices or methods of any prior embodiment, wherein the        spacers are configured, such that the filling factor multiplies        the Young's modulus of the spacer is in the range of 120 MPa to        150 MPa.    -   106. The devices or methods of any prior embodiment, wherein the        device further comprises a dry reagent coated on one or both        plates.    -   107. The devices or methods of any prior embodiment, wherein the        device further comprises, on one or both plates, a dry binding        site that has a predetermined area, wherein the dry binding site        binds to and immobilizes an analyte in the sample.    -   108. The devices or methods of any prior embodiment, wherein the        device further comprises, on one or both plates, a releasable        dry reagent and a release time control material that delays the        time that the releasable dry regent is released into the sample.    -   109. The device of any prior embodiment, wherein the release        time control material delays the time that the dry regent starts        is released into the sample by at least 3 seconds.    -   110. The device of any prior embodiment, wherein the regent        comprises anticoagulant and/or staining reagent(s)    -   111. The device of any prior embodiment, wherein the reagent        comprises cell lysing reagent(s)    -   112. The devices or methods of any prior embodiment, wherein the        device further comprises, on one or both plates, one or a        plurality of dry binding sites and/or one or a plurality of        reagent sites.    -   113. The device of any prior device embodiment, wherein the        analyte comprises a molecule (e.g., a protein, peptides, DNA,        RNA, nucleic acid, or other molecule), cells, tissues, viruses,        and nanoparticles with different shapes.    -   114. The device of any prior device embodiment, wherein the        analyte comprises white blood cells, red blood cells and        platelets.    -   115. The device of any prior device embodiment, wherein the        analyte is stained.    -   116. The devices or methods of any prior embodiment, wherein the        spacers regulating the layer of uniform thickness have a filling        factor of at least 1%, wherein the filling factor is the ratio        of the spacer area in contact with the layer of uniform        thickness to the total plate area in contact with the layer of        uniform thickness.    -   117. The devices or methods of any prior embodiment, wherein for        spacers regulating the layer of uniform thickness, the Young's        modulus of the spacers times the filling factor of the spacers        is equal or larger than 10 MPa, wherein the filling factor is        the ratio of the spacer area in contact with the layer of        uniform thickness to the total plate area in contact with the        layer of uniform thickness.    -   118. The devices or methods of any prior embodiment, wherein for        a flexible plate, the thickness of the flexible plate times the        Young's modulus of the flexible plate is in the range 60 to 750        GPa-um.    -   119. The devices or methods of any prior embodiment, wherein for        a flexible plate, the fourth power of the inter-spacer-distance        (ISD) divided by the thickness of the flexible plate (h) and the        Young's modulus (E) of the flexible plate, ISD⁴/(hE), is equal        to or less than 10⁶ um³/GPa,    -   120. The devices or methods of any prior embodiment, wherein one        or both plates comprises a location marker, either on a surface        of or inside the plate, that provide information of a location        of the plate.    -   131. The devices or methods of any prior embodiment, wherein        each spacer has the ratio of the lateral dimension of the spacer        to its height is at least 1.    -   132. The devices or methods of any prior embodiment, wherein the        minimum lateral dimension of spacer is less than or        substantially equal to the minimum dimension of an analyte in        the sample.    -   133. The devices or methods of any prior embodiment, wherein the        minimum lateral dimension of spacer is in the range of 0.5 um to        100 um.    -   134. The devices or methods of any prior embodiment, wherein the        minimum lateral dimension of spacer is in the range of 0.5 um to        10 um.    -   135. The devices or methods of any prior embodiment, wherein the        sample is blood.    -   136. The devices or methods of any prior embodiment, wherein the        sample is whole blood without dilution by liquid.    -   137. The devices or methods of any prior embodiment, wherein the        sample is a biological sample selected from amniotic fluid,        aqueous humour, vitreous humour, blood (e.g., whole blood,        fractionated blood, plasma or serum), breast milk, cerebrospinal        fluid (CSF), cerumen (earwax), chyle, chime, endolymph,        perilymph, feces, breath, gastric acid, gastric juice, lymph,        mucus (including nasal drainage and phlegm), pericardial fluid,        peritoneal fluid, pleural fluid, pus, rheum, saliva, exhaled        breath condensates, sebum, semen, sputum, sweat, synovial fluid,        tears, vomit, and urine.    -   138. The devices or methods of any prior embodiment, wherein the        sample is a biological sample, an environmental sample, a        chemical sample, or clinical sample.    -   139. The devices or methods of any prior embodiment, wherein the        spacers have a pillar shape, and the sidewall corners of the        spacers have a round shape with a radius of curvature at least 1        □m.    -   140. The devices or methods of any prior embodiment, wherein the        spacers have a density of at least 100/mm².    -   141. The devices or methods of any prior embodiment, wherein the        spacers have a density of at least 1000/mm².    -   142. The devices or methods of any prior embodiment, wherein at        least one of the plates is transparent.    -   143. The devices or methods of any prior embodiment, wherein at        least one of the plates is made from a flexible polymer.    -   144. The devices or methods of any prior embodiment, wherein,        for a pressure that compresses the plates, the spacers are not        compressible and/or, independently, only one of the plates is        flexible.    -   145. The device of any of any prior embodiment, wherein the        flexible plate has a thickness in the range of 10 um to 200 um.    -   146. The devices or methods of any prior embodiment, wherein the        variation is less than 30%.    -   147. The devices or methods of any prior embodiment, wherein the        variation is less than 10%.    -   148. The devices or methods of any prior embodiment, wherein the        variation is less than 5%.    -   149. The devices or methods of any prior embodiment, wherein the        first and second plates are connected and are configured to be        changed from the open configuration to the closed configuration        by folding the plates.    -   150. The devices or methods of any prior embodiment, wherein the        first and second plates are connected by a hinge and are        configured to be changed from the open configuration to the        closed configuration by folding the plates along the hinge.    -   151. The devices or methods of any prior embodiment, wherein the        first and second plates are connected by a hinge that is a        separate material to the plates, and are configured to be        changed from the open configuration to the closed configuration        by folding the plates along the hinge    -   152. The devices or methods of any prior embodiment, wherein the        first and second plates are made in a single piece of material        and are configured to be changed from the open configuration to        the closed configuration by folding the plates.    -   153. The devices or methods of any prior embodiment, wherein the        layer of uniform thickness sample is uniform over a lateral area        that is at least 1 mm².    -   154. The devices or methods of any prior embodiment, wherein the        device is configured to analyze the sample in 60 seconds or        less.    -   155. The devices or methods of any prior embodiment, wherein at        the closed configuration, the final sample thickness device is        configured to analyze the sample in 60 seconds or less.    -   156. The devices or methods of any prior embodiment, wherein at        the closed configuration, the final sample thickness device is        configured to analyze the sample in 10 seconds or less.    -   157. The devices or methods of any prior embodiment, wherein the        dry binding site comprises a capture agent.    -   158. The devices or methods of any prior embodiment, wherein the        dry binding site comprises an antibody or nucleic acid.    -   159. The devices or methods of any prior embodiment, wherein the        releasable dry reagent is a labeled reagent.    -   160. The devices or methods of any prior embodiment, wherein the        releasable dry reagent is a fluorescently-labeled reagent.    -   161. The devices or methods of any prior embodiment, wherein the        releasable dry reagent is a fluorescently-labeled antibody.    -   162. The devices or methods of any prior embodiment, wherein the        releasable dry reagent is a cell stain.    -   163. The devices or methods of any prior embodiment, wherein the        releasable dry reagent is a cell lysing.    -   164. The devices or methods of any prior embodiment, wherein the        detector is an optical detector that detects an optical signal.    -   165. The devices or methods of any prior embodiment, wherein the        detector is an electric detector that detect electrical signal.    -   166. The device of any prior device embodiment, wherein the        spacing are fixed on a plate by directly embossing the plate or        injection molding of the plate.    -   167. The device of any prior device embodiment, wherein the        materials of the plate and the spacers are selected from        polystyrene, PMMA, PC, COC, COP, or another plastic.    -   168. A system for rapidly analyzing a sample using a mobile        phone comprising:        -   (a) a device of any prior embodiment;        -   (b) a mobile communication device comprising:            -   i. one or a plurality of cameras for the detecting                and/or imaging the sample;            -   ii. electronics, signal processors, hardware and                software for receiving and/or processing the detected                signal and/or the image of the sample and for remote                communication; and        -   (c) a light source from either the mobile communication            device or an external source;        -   wherein the detector in the devices or methods of any prior            embodiment is provided by the mobile communication device,            and detects an analyte in the sample at the closed            configuration.    -   169. The system of any prior system embodiment, wherein one of        the plates has a binding site that binds an analyte, wherein at        least part of the uniform sample thickness layer is over the        binding site, and is substantially less than the average lateral        linear dimension of the binding site.    -   170. The system of any prior system embodiment, further        comprising:        -   (d) a housing configured to hold the sample and to be            mounted to the mobile communication device.    -   171. The system of any prior system embodiment, wherein the        housing comprises optics for facilitating the imaging and/or        signal processing of the sample by the mobile communication        device, and a mount configured to hold the optics on the mobile        communication device.    -   172. The system of any prior system embodiment, wherein an        element of the optics in the housing is movable relative to the        housing.    -   173. The system of any prior system embodiment, wherein the        mobile communication device is configured to communicate test        results to a medical professional, a medical facility or an        insurance company.    -   174. The system of any prior system embodiment, wherein the        mobile communication device is further configured to communicate        information on the test and the subject with the medical        professional, medical facility or insurance company.    -   175. The system of any prior system embodiment, wherein the        mobile communication device is further configured to communicate        information of the test to a cloud network, and the cloud        network process the information to refine the test results.    -   176. The system of any prior system embodiment, wherein the        mobile communication device is further configured to communicate        information of the test and the subject to a cloud network, the        cloud network process the information to refine the test        results, and the refined test results will send back the        subject.    -   177. The system of any prior system embodiment, wherein the        mobile communication device is configured to receive a        prescription, diagnosis or a recommendation from a medical        professional.    -   178. The system of any prior system embodiment, wherein the        mobile communication device is configured with hardware and        software to:        -   (a) capture an image of the sample;        -   (b) analyze a test location and a control location in in            image; and        -   (c) compare a value obtained from analysis of the test            location to a threshold value that characterizes the rapid            diagnostic test.    -   179. The system of any prior system embodiment, wherein at least        one of the plates comprises a storage site in which assay        reagents are stored.    -   180. The system of any prior system embodiment, at least one of        the cameras reads a signal from the device.    -   181. The system of any prior system embodiment, wherein the        mobile communication device communicates with the remote        location via a wifi or cellular network.    -   182. The system of any prior system embodiment, wherein the        mobile communication device is a mobile phone.    -   183. A method for rapidly analyzing an analyte in a sample using        a mobile phone, comprising:        -   (a) depositing a sample on the device of any prior system            embodiment;        -   (b) assaying an analyte in the sample deposited on the            device to generate a result; and        -   (c) communicating the result from the mobile communication            device to a location remote from the mobile communication            device.    -   184. The method of any prior embodiments embodiment, wherein the        analyte comprises a molecule (e.g., a protein, peptides, DNA,        RNA, nucleic acid, or other molecule), cells, tissues, viruses,        and nanoparticles with different shapes.    -   185. The method of any prior embodiment, wherein the analyte        comprises white blood cell, red blood cell and platelets.    -   186. The method of any prior embodiment, wherein the assaying        comprises performing a white blood cells differential assay.    -   187. The method of any prior embodiments embodiment, wherein the        method comprises:        -   analyzing the results at the remote location to provide an            analyzed result; and        -   communicating the analyzed result from the remote location            to the mobile communication device.    -   188. The method of any prior embodiment, wherein the analysis is        done by a medical professional at a remote location.    -   189. The method of any prior embodiment, wherein the mobile        communication device receives a prescription, diagnosis or a        recommendation from a medical professional at a remote location.    -   190. The method of any prior embodiment, wherein the sample is a        bodily fluid.    -   191. The method of any prior embodiment, wherein the bodily        fluid is blood, saliva or urine.    -   192. The method of any prior embodiment, wherein the sample is        whole blood without dilution by a liquid.    -   193. The method of any prior embodiment, wherein the assaying        step comprises detecting an analyte in the sample.    -   194. The method of any prior embodiment, wherein the analyte is        a biomarker.    -   195. The method of any prior embodiment, wherein the analyte is        a protein, nucleic acid, cell, or metabolite.    -   196. The method of any prior embodiment, wherein the method        comprises counting the number of red blood cells.    -   197. The method of any of any prior embodiment, wherein the        method comprises counting the number of white blood cells.    -   198. The method of any prior embodiment, wherein method        comprises staining the cells in the sample and counting the        number of neutrophils, lymphocytes, monocytes, eosinophils and        basophils.    -   199. The method of any prior embodiments embodiment, wherein the        assay done in step (b) is a binding assay or a biochemical        assay.    -   200. A method for analyzing a sample comprising:        -   obtaining a device of any prior device embodiment;        -   depositing the sample onto one or both pates of the device;        -   placing the plates in a closed configuration and applying an            external force over at least part of the plates; and        -   analyzing the in the layer of uniform thickness while the            plates are the closed configuration.    -   201. The devices or methods of any prior embodiment, wherein the        first plate further comprises, on its surface, a first        predetermined assay site and a second predetermined assay site,        wherein the distance between the edges of the assay site is        substantially larger than the thickness of the uniform thickness        layer when the plates are in the closed position, wherein at        least a part of the uniform thickness layer is over the        predetermined assay sites, and wherein the sample has one or a        plurality of analytes that are capable of diffusing in the        sample.    -   202. The devices or methods of any prior embodiment, wherein the        first plate has, on its surface, at least three analyte assay        sites, and the distance between the edges of any two neighboring        assay sites is substantially larger than the thickness of the        uniform thickness layer when the plates are in the closed        position, wherein at least a part of the uniform thickness layer        is over the assay sites, and wherein the sample has one or a        plurality of analytes that are capable of diffusing in the        sample.    -   203. The devices or methods of any prior embodiment, wherein the        first plate has, on its surface, at least two neighboring        analyte assay sites that are not separated by a distance that is        substantially larger than the thickness of the uniform thickness        layer when the plates are in the closed position, wherein at        least a part of the uniform thickness layer is over the assay        sites, and wherein the sample has one or a plurality of analytes        that are capable of diffusing in the sample.    -   204. The devices or methods of any prior embodiment, wherein the        analyte assay area is between a pair of electrodes.    -   205. The devices or methods of any prior embodiment, wherein the        assay area is defined by a patch of dried reagent.    -   206. The devices or methods of any prior embodiment, wherein the        assay area binds to and immobilizes the analyte    -   207. The devices or methods of any prior embodiment, wherein the        assay area is defined by a patch of binding reagent that, upon        contacting the sample, dissolves into the sample, diffuses in        the sample, and binds to the analyte.    -   208. The devices or methods of any prior embodiment, wherein the        inter-spacer distance is in the range of 14 □m to 200 □m.    -   209. The devices or methods of any prior embodiment, wherein the        inter-spacer distance is in the range of 7 □m to 20 □m.    -   210. The devices or methods of any prior embodiment, wherein the        spacers are pillars with a cross-sectional shape selected from        round, polygonal, circular, square, rectangular, oval,        elliptical, or any combination of the same.    -   211. The devices or methods of any prior embodiment, wherein the        spacers have a pillar shape and have a substantially flat top        surface, wherein, for each spacer, the ratio of the lateral        dimension of the spacer to its height is at least 1.    -   212. The devices or methods of any prior embodiment, wherein the        spacers have a pillar shape, and the sidewall corners of the        spacers have a round shape with a radius of curvature at least 1        □m.    -   213. The devices or methods of any prior embodiment, wherein the        spacers have a density of at least 1000/mm².    -   214. The devices or methods of any prior embodiment, wherein at        least one of the plates is transparent.    -   215. The devices or methods of any prior embodiment, wherein at        least one of the plates is made from a flexible polymer.    -   216. The devices or methods of any prior embodiment, wherein        only one of the plates is flexible.        The device of any prior embodiment, wherein the        area-determination device is a camera.

The area-determination device comprises an area in the sample contactarea of a plate, wherein the area is less than 1/100, 1/20, 1/10, ⅙, ⅕,¼, ⅓, ½, ⅔ of the sample contact area, or in a range between any of thetwo values.

The area-determination device comprises a camera and an area in thesample contact area of a plate, wherein the area is in contact with thesample.

The devices or methods of any prior embodiment, wherein the deformablesample comprises a liquid sample.The devices or methods of any prior embodiment, wherein the imprecisionforce has a variation at least 30% of the total force that actually isapplied.The devices or methods of any prior embodiment, wherein the imprecisionforce has a variation at least 20%, 30%, 40%, 50%, 60, 70%, 80%, 90%100%, 150%, 200%, 300%, 500%, or in a range of any two values, of thetotal force that actually is applied.

-   -   217. The device or method of any prior embodiment, wherein        spacers have a flat top.    -   218. The device or method of any prior embodiment, wherein the        device is further configured to have, after the pressing force        is removed, a sample thickness that is substantially the same in        thickness and uniformity as that when the force is applied.    -   219. The device or method of any prior embodiment, wherein the        imprecise force is provided by human hand.    -   220. The device or method of any prior embodiment, wherein the        inter spacer distance is substantially constant.    -   221. The device or method of any prior embodiment, wherein the        inter spacer distance is substantially periodic in the area of        the uniform sample thickness area.    -   222. The device or method of any prior embodiment, wherein the        multiplication product of the filling factor and the Young's        modulus of the spacer is 2 MPa or larger.    -   223. The device or method of any prior embodiment, wherein the        force is applied by hand directly or indirectly.    -   224. The device or method of any prior embodiment, wherein the        force applied is in the range of 5 N to 20 N.    -   225. The device or method of any prior embodiment wherein the        highly uniform layer has a thickness that varies by less than        15%, 10%, or 5% of an average thickness.    -   226. The device or method of any prior embodiment, wherein the        imprecise force is applied by pinching the device between a        thumb and forefinger.    -   227. The device or method of any prior embodiment, wherein the        predetermined sample thickness is larger than the spacer height.    -   228. The device or method of any prior embodiment, wherein the        device holds itself in the closed configuration after the        pressing force has been removed.    -   229. The device or method of any prior embodiment, wherein the        uniform thickness sample layer area is larger than that area        upon which the pressing force is applied.    -   230. The device or method of any prior embodiment, wherein the        spacers do not significantly deform during application of the        pressing force.    -   231. The device or method of any prior embodiment, wherein the        pressing force is not predetermined beforehand and is not        measured.    -   232. The device of any prior device embodiment, wherein the        analyte comprises a molecule (e.g., a protein, peptides, DNA,        RNA, nucleic acid, or other molecule), cells, tissues, viruses,        and nanoparticles with different shapes.    -   233. The device of any prior device embodiment, wherein the        analyte comprises white blood cells, red blood cells and        platelets.    -   234. The device of any prior device embodiment, wherein the        analyte is stained.    -   235. The method or device of any prior embodiment, wherein the        inter spacer distance (SD) is equal or less than about 120 um        (micrometer).    -   236. The method or device of any prior embodiment, wherein the        inter spacer distance (SD) is equal or less than about 100 um        (micrometer).    -   237. The method or device of any prior embodiment, wherein the        fourth power of the inter-spacer-distance (ISD) divided by the        thickness (h) and the Young's modulus (E) of the flexible plate        (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.    -   238. The method or device of any prior embodiment, wherein the        fourth power of the inter-spacer-distance (ISD) divided by the        thickness (h) and the Young's modulus (E) of the flexible plate        (ISD⁴/(hE)) is 5×10⁵ um³/GPa or less.    -   239. The method or device of any prior embodiment, wherein the        spacers have pillar shape, a substantially flat top surface, a        predetermined substantially uniform height, and a predetermined        constant inter-spacer distance that is at least about 2 times        larger than the size of the analyte, wherein the Young's modulus        of the spacers times the filling factor of the spacers is equal        or larger than 2 MPa, wherein the filling factor is the ratio of        the spacer contact area to the total plate area, and wherein,        for each spacer, the ratio of the lateral dimension of the        spacer to its height is at least 1 (one).    -   240. The method or device of any prior embodiment, wherein the        spacers have pillar shape, a substantially flat top surface, a        predetermined substantially uniform height, and a predetermined        constant inter-spacer distance that is at least about 2 times        larger than the size of the analyte, wherein the Young's modulus        of the spacers times the filling factor of the spacers is equal        or larger than 2 MPa, wherein the filling factor is the ratio of        the spacer contact area to the total plate area, and wherein,        for each spacer, the ratio of the lateral dimension of the        spacer to its height is at least 1 (one), wherein the fourth        power of the inter-spacer-distance (ISD) divided by the        thickness (h) and the Young's modulus (E) of the flexible plate        (ISD⁴/(hE)) is 5×10⁶ um³/GPa or less.    -   241. The device of any prior device embodiment, wherein the        ratio of the inter-spacing distance of the spacers to the        average width of the spacer is 2 or larger, and the filling        factor of the spacers multiplied by the Young's modulus of the        spacers is 2 MPa or larger.    -   242. The method or device of any prior embodiment, wherein the        analytes is the analyte in 5 detection of proteins, peptides,        nucleic acids, synthetic compounds, and inorganic compounds.    -   243. The method or device of any prior embodiment, wherein the        sample is a biological sample selected from amniotic fluid,        aqueous humour, vitreous humour, blood (e.g., whole blood,        fractionated blood, plasma or serum), breast milk, cerebrospinal        fluid (CSF), cerumen (earwax), chyle, chime, endolymph,        perilymph, feces, breath, gastric acid, gastric juice, lymph,        mucus (including nasal drainage and phlegm), pericardial fluid,        peritoneal fluid, pleural fluid, pus, rheum, saliva, exhaled        breath condensates, sebum, semen, sputum, sweat, synovial fluid,        tears, vomit, and urine.    -   244. The method or device of any prior embodiment, wherein the        spacers have a shape of pillars and a ratio of the width to the        height of the pillar is equal or larger than one.    -   245. The method of any prior embodiment, wherein the sample that        is deposited on one or both of the plates has an unknown volume.    -   246. The method or device of any prior embodiment, wherein the        samples is for the detection, purification and quantification of        chemical compounds or biomolecules that correlates with the        stage of certain diseases.    -   247. The method or device of any prior embodiment, wherein the        samples is related to infectious and parasitic disease,        injuries, cardiovascular disease, cancer, mental disorders,        neuropsychiatric disorders, pulmonary diseases, renal diseases,        and other and organic diseases.    -   248. The method or device of any prior embodiment, wherein the        samples is related to the detection, purification and        quantification of microorganism.    -   249. The method or device of any prior embodiment, wherein the        samples is related to virus, fungus and bacteria from        environment, e.g., water, soil, or biological samples.    -   250. The method or device of any prior embodiment, wherein the        samples is related to the detection, quantification of chemical        compounds or biological samples that pose hazard to food safety        or national security, e.g. toxic waste, anthrax.    -   251. The method or device of any prior embodiment, wherein the        samples is related to quantification of vital parameters in        medical or physiological monitor.    -   252. The method or device of any prior embodiment, wherein the        samples is related to glucose, blood, oxygen level, total blood        count.    -   253. The method or device of any prior embodiment, wherein the        samples is related to the detection and quantification of        specific DNA or RNA from biosamples.    -   254. The method or device of any prior embodiment, wherein the        samples is related to the sequencing and comparing of genetic        sequences in DNA in the chromosomes and mitochondria for genome        analysis.    -   255. The method or device of any prior embodiment, wherein the        samples is related to detect reaction products, e.g., during        synthesis or purification of pharmaceuticals.    -   256. The method or device of any prior embodiment, wherein the        samples is cells, tissues, bodily fluids, and stool.    -   257. The method or device of any prior embodiment, wherein the        sample is the sample in the detection of proteins, peptides,        nucleic acids, synthetic compounds, inorganic compounds.    -   258. The method or device of any prior embodiment, wherein the        sample is the sample in the fields of human, veterinary,        agriculture, foods, environments, and drug testing.    -   259. The method or device of any prior embodiment, wherein the        sample is a biological sample is selected from blood, serum,        plasma, a nasal swab, a nasopharyngeal wash, saliva, urine,        gastric fluid, spinal fluid, tears, stool, mucus, sweat, earwax,        oil, a glandular secretion, cerebral spinal fluid, tissue,        semen, vaginal fluid, interstitial fluids derived from tumorous        tissue, ocular fluids, spinal fluid, a throat swab, breath,        hair, finger nails, skin, biopsy, placental fluid, amniotic        fluid, cord blood, lymphatic fluids, cavity fluids, sputum, pus,        microbiota, meconium, breast milk, exhaled condensate        nasopharyngeal wash, throat swab, stool samples, hair, finger        nail, ear wax, breath, connective tissue, muscle tissue, nervous        tissue, epithelial tissue, cartilage, cancerous sample, or bone.    -   260. The devices or methods of any prior embodiment, wherein the        spacers regulating the layer of uniform thickness have a filling        factor of at least 1%, wherein the filling factor is the ratio        of the spacer area in contact with the layer of uniform        thickness to the total plate area in contact with the layer of        uniform thickness.

Manufacturing of Q-Card

MA1. An embodiment of the Q-Card comprising: a first plate, a secondplate, and a hinge, wherein

-   -   i. the first plate, that is about 200 nm to 1500 nm thick,        comprises, on its inner surface, (a) a sample contact area for        contacting a sample, and (b) a sample overflow dam that        surrounds the sample contact area is configured to present a        sample flow outside of the dam;    -   ii. the second plate is 10 um to 250 um thick and comprises, on        its inner surface, (a) a sample contact area for contacting a        sample, and (b) spacers on the sample contact area;    -   iii. the hinge that connect the first and the second plates; and        wherein the first and second plate are movable relative to each        other around the axis of the hinge.        MA2. An embodiment of the Q-Card comprising: a first plate, a        second plate, and a hinge, wherein    -   i. the first plate, that is about 200 nm to 1500 nm thick,        comprises, on its inner surface, (a) a sample contact area for        contacting a sample, (b) a sample overflow dam that surrounds        the sample contact area is configured to present a sample flow        outside of the dam, and (c) spacers on the sample contact area;    -   ii. the second plate, that is 10 urn to 250 urn thick,        comprises, on its inner surface, a sample contact area for        contacting a sample;    -   iii. the hinge that connect the first and the second plates; and        wherein the first and second plate are movable relative to each        other around the axis of the hinge.        MA3. An embodiment of the Q-Card comprising: a first plate, a        second plate, and a hinge, wherein    -   i. the first plate, that is about 200 nm to 1500 nm thick,        comprises, on its inner surface, (a) a sample contact area for        contacting a sample, and (b) spacers on the sample contact area;    -   ii. the second plate, that is 10 urn to 250 urn thick,        comprises, on its inner surface, (a) a sample contact area for        contacting a sample, and (b) a sample overflow dam that        surrounds the sample contact area is configured to present a        sample flow outside of the dam, and;    -   iii. the hinge that connect the first and the second plates; and        wherein the first and second plate are movable relative to each        other around the axis of the hinge.        MA4 An embodiment of the Q-Card comprising: a first plate, a        second plate, and a hinge, wherein    -   i. the first plate, that is about 200 nm to 1500 nm thick,        comprises, on its inner surface, a sample contact area for        contacting a sample;    -   ii. the second plate, that is 10 urn to 250 urn thick,        comprises, on its inner surface, (a) a sample contact area for        contacting a sample, (b) a sample overflow dam that surrounds        the sample contact area is configured to present a sample flow        outside of the dam, and (c) spacers on the sample contact area;        and    -   iii. the hinge that connect the first and the second plates; and        wherein the first and second plate are movable relative to each        other around the axis of the hinge.        M1 An embodiment of a method for fabricating the Q-Card of any        embodiments of MA1 to MA4, comprising:

(a) injection molding of the first plate,

(b) nanoimprinting or extrusion printing of the second plate.

M2 An embodiment of a method for fabricating the Q-Card of anyembodiments of MA1 to MA4, comprising:

(a) Laser cutting the first plate,

(b) nanoimprinting or extrusion printing of the second plate.

M3 An embodiment of a method for fabricating the Q-Card of anyembodiments of MA1 to MA4, comprising:

(a) Injection molding and laser cutting the first plate,

(b) nanoimprinting or extrusion printing of the second plate.

M4 An embodiment of a method for fabricating the Q-Card of anyembodiments of MA1 to MA4, comprising: nanoimprinting or extrusionprinting to fabricated both the first and the second plate.M5 An embodiment of a method for fabricating the Q-Card of anyembodiments of MA1 to MA4, comprising: fabricating the first plate orthe second plate, using injection molding, laser cutting the firstplate, nanoimprinting, extrusion printing, or a combination of thereof.The method of any embodiments of M1-M5, wherein the method furthercomprises a step of attach the hinge on the first and the second platesafter the fabrication of the first and second plates.

Device and System for Collecting and Analyzing Vapor Condensate,Particularly Exhaled Breath Condensate, as Well Method of Using the Same

A device is provided herein for collecting and analyzing vaporcondensate (VC) sample, comprising:

a collection plate, a cover plate, and spacers, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates has, on its respective inner surface, a        sample contact area for contacting a vapor condensate (VC)        sample that contains an analyte;    -   iv. the spacers are fixed to the respective inner surface of one        or both of the plates, and have a predetermined substantially        uniform height and a predetermined constant inter-spacer        distance and wherein at least one of the spacers is inside the        sample contact area;        -   wherein one of the configurations is an open configuration,            in which: the two plates are either completely or partially            separated apart, the spacing between the plates is not            regulated by the spacers, and the VC sample is deposited on            one or both of the plates; and        -   wherein another of the configurations is a closed            configuration which is configured after the VC sample            deposition in the open configuration; and in the closed            configuration: at least a part of the VC sample is between            the two plates and in contact with the two plates, and has a            highly uniform thickness that is regulated by the spacers            and the two sample surfaces of the plates and is equal to or            less than 30 □m with a small variation.

Another device is provided herein for collecting and analyzing vaporcondensate (VC) sample, comprising:

a collection plate and a cover plate, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible; and    -   iii. each of the plates has, on its respective surface, a sample        contact area for contacting a vapor condensate (VC) sample that        contains an analyte;        -   wherein one of the configurations is an open configuration,            in which: the two plates are either completely or partially            separated apart, and the VC sample is deposited on one or            both of the plates; and        -   wherein another of the configurations is a closed            configuration which is configured after the VC sample            deposition in the open configuration; and in the closed            that is in contact with the layer of uniform thickness. In            some embodiments, the thickness of the flexible plate times            the Young's modulus of the flexible plate is in the range 60            to 750 GPa-um, e.g., 100 to 300 GPa-um, 300 to 550 GPa-um,            or 550 to 750 GPa-um. In some embodiments, for a flexible            plate, the fourth power of the inter-spacer-distance (ISD)            divided by the thickness of the flexible plate (h) and the            Young's modulus (E) of the flexible plate, ISD4/(hE), is            equal to or less than 106 um3/GPa, e.g., less than 105            um3/GPa, less than 104 um3/GPa or less than 103 um3/GPa.

In some embodiments, one or both plates comprises a location markereither on a surface of or inside the plate, that provide information ofa location of the plate, e.g., a location that is going to be analyzedor a location onto which the blood should be deposited. In some cases,one or both plates may comprise a scale marker, either on a surface ofor inside the plate, that provides information of a lateral dimension ofa structure of the blood sample and/or the plate. In some embodiments,one or both plates comprises an imaging marker, either on surface of orinside the plate that assists an imaging of the sample. For example, theimaging marker could help focus the imaging device or direct the imagingdevice to a location on the device. In some embodiments, the spacers canfunction as a location marker, a scale marker, an imaging marker, or anycombination of thereof.

In some embodiments, on one of the sample surface, it further comprisesan enclosure-spacer that encloses a partial or entire VC samplesdeposited on the collection plate.

In some embodiments, the highly uniform thickness has a value equal toor less than 0.5 um. In some embodiments, the highly uniform thicknesshas a value in the range of 0.5 um to 1 um, 1 um to 2 um, 2 um to 10 um,10 um to 20 um or 20 um to 30 um.

In some embodiments, the thickness of the at least a part of VC sampleat the closed configuration is larger than the thickness of VC sampledeposited on the collection plate at an open configuration.

In some embodiments, the thickness of the at least a part of VC sampleat the closed configuration is less than the thickness of VC sampledeposited on the collection plate at an open configuration.

In some embodiments, wherein the spacers are fixed on a plate bydirectly embossing the plate or injection molding of the plate.

In some embodiments, wherein the materials of the plate and the spacersare selected from polystyrene, PMMA, PC, COC, COP, or another plastic.

In some embodiments, the inter-spacer spacing in the range of 1 um to 50um, 50 um to 100 um, 100 um to 200 um or 200 um to 1000 um.

In some embodiments, the VC sample is an exhaled breath condensate froma human or an animal.

In some embodiments, the spacers regulating the layer of uniformthickness have a filling factor of at least 1%, wherein the fillingfactor is the ratio of the spacer area in contact with the layer ofuniform thickness to the total plate area in contact with the layer ofuniform thickness.

In some embodiments, for spacers regulating the layer of uniformthickness, the Young's modulus of the spacers times the filling factorof the spacers is equal or larger than 10 MPa, wherein the fillingfactor is the ratio of the spacer area in contact with the layer ofuniform thickness to the total plate area in contact with the layer ofuniform thickness.

In some embodiments, for a flexible plate, the thickness of the flexibleplate times the Young's modulus of the flexible plate is in the range 60to 750 GPa-um.

In some embodiments, for a flexible plate, the fourth power of theinter-spacer-distance (ISD) divided by the thickness of the flexibleplate (h) and the Young's modulus (E) of the flexible plate, ISD4/(hE),is equal to or less than 106 um3/GPa,

In some embodiments, one or both plates comprises a location marker,either on a surface of or inside the plate, that provide information ofa location of the plate.

In some embodiments, one or both plates comprises a scale marker, eitheron a surface of or inside the plate, that provide information of alateral dimension of a structure of the sample and/or the plate.

In some embodiments, one or both plates comprises an imaging marker,either on surface of or inside the plate, that assists an imaging of thesample.

In some embodiments, the spacers functions as a location marker, a scalemarker, an imaging marker, or any combination of thereof.

In some embodiments, the average thickness of the layer of uniformthickness is about equal to a minimum dimension of an analyte in thesample.

In some embodiments, the inter-spacer distance is 1 μm or less, 5 μm orless, 7 μm or less, 10 μm or less, 20 μm or less, 30 μm or less, 40 μmor less, 50 μm or less, 60 μm or less, 70 μm or less, 80 μm or less, 90μm or less, 100 μm or less, 200 μm or less, 300 μm or less, 400 μm orless, or in a range between any two of the values.

In some embodiments, the inter-spacer distance is substantiallyperiodic.

In some embodiments, the inter-spacer distance is aperiodic.

In some embodiments, the spacers are pillars with a cross-sectionalshape selected from round, polygonal, circular, square, rectangular,oval, elliptical, or any combination of the same.

In some embodiments, the spacers have are pillar shape and have asubstantially flat top surface, wherein, for each spacer, the ratio ofthe lateral dimension of the spacer to its height is at least 1.

In some embodiments, each spacer has the ratio of the lateral dimensionof the spacer to its height is at least 1.

In some embodiments, the minimum lateral dimension of spacer is lessthan or substantially equal to the minimum dimension of an analyte inthe sample.

In some embodiments, the minimum lateral dimension of spacer is in therange of 0.5 um to 100 um.

In some embodiments, the minimum lateral dimension of spacer is in therange of 0.5 um to 10 um.

In some embodiments, the spacers have a density of at least 100/mm2. Insome embodiments, the spacers have a density of at least 1000/mm2. Insome embodiments, at least one of the plates is transparent.

In some embodiments, at least one of the plates is made from a flexiblepolymer.

In some embodiments, for a pressure that compresses the plates, thespacers are not compressible and/or, independently, only one of theplates is flexible.

In some embodiments, the flexible plate has a thickness in the range of10 um to 200 um (e.g. about 10 um, 25 um, 50 um, 75 um, 100 um, 125 um,150 um, 175 um).

In some embodiments, the variation is less than 30%, 10%, 5%, 3% or 1%.

In some embodiments, the first and second plates are connected and areconfigured to be changed from the open configuration to the closedconfiguration by folding the plates.

In some embodiments, the first and second plates are connected by ahinge and are configured to be changed from the open configuration tothe closed configuration by folding the plates along the hinge.

In some embodiments, the first and second plates are connected by ahinge that is a separate material to the plates, and are configured tobe changed from the open configuration to the closed configuration byfolding the plates along the hinge

In some embodiments, the first and second plates are made in a singlepiece of material and are configured to be changed from the openconfiguration to the closed configuration by folding the plates.

In some embodiments, the layer of uniform thickness sample is uniformover a lateral area that is at least 100 um².

In some embodiments, the layer of uniform thickness sample is uniformover a lateral area that is at least 1 mm².

In some embodiments, the device is configured to analyze the sample in60 seconds or less.

In some embodiments, at the closed configuration, the final samplethickness device is configured to analyze the sample in 60 seconds orless.

In some embodiments, the device further comprises, on one or both of theplates, one or a plurality of amplification sites that are each capableof amplifying a signal from the analyte or a label of the analyte whenthe analyte or label is within 500 nm from an amplification site.

In some embodiments, at the closed configuration, the final samplethickness device is configured to analyze the sample in 10 seconds orless.

In some embodiments, the dry binding site comprises a capture agent.

In some embodiments, the dry binding site comprises an antibody ornucleic acid. In some embodiments, the releasable dry reagent is alabeled reagent. In some embodiments, the releasable dry reagent is afluorescently-labeled reagent. In some embodiments, the releasable dryreagent is a dye. In some embodiments, the releasable dry reagent is abeads. In some embodiments, the releasable dry reagent is a quantum dot.In some embodiments, the releasable dry reagent is afluorescently-labeled antibody.

In some embodiments, the first plate further comprises, on its surface,a first predetermined assay site and a second predetermined assay site,wherein the distance between the edges of the assay site issubstantially larger than the thickness of the uniform thickness layerwhen the plates are in the closed position, wherein at least a part ofthe uniform thickness layer is over the predetermined assay sites, andwherein the sample has one or a plurality of analytes that are capableof diffusing in the sample.

In some embodiments, the first plate has, on its surface, at least threeanalyte assay sites, and the distance between the edges of any twoneighboring assay sites is substantially larger than the thickness ofthe uniform thickness layer when the plates are in the closed position,wherein at least a part of the uniform thickness layer is over the assaysites, and wherein the sample has one or a plurality of analytes thatare capable of diffusing in the sample.

In some embodiments, the first plate has, on its surface, at least twoneighboring analyte assay sites that are not separated by a distancethat is substantially larger than the thickness of the uniform thicknesslayer when the plates are in the closed position, wherein at least apart of the uniform thickness layer is over the assay sites, and whereinthe sample has one or a plurality of analytes that are capable ofdiffusing in the sample.

In some embodiments, the releasable dry reagent is a cell stain. In someembodiments, the device further comprises a detector that is an opticaldetector for detecting an optical signal. In some embodiments, thedevice further comprises a detector that is an electrical detector fordetecting an electric signal.

In some embodiments, the device comprises discrete spacers that are notfixed to any of the plates, wherein at the closed configuration, thediscrete spacers are between the inner surfaces of the two plates, andthe thickness of the sample is confined by the inner surfaces of the twoplates, and regulated by the discrete spacers and the plates.

In some embodiments, the device further comprises a binding site thathas a chemical sensor that is made from a material selected from thegroup consisting of: silicon nanowire (Si NW); single-walled carbonnanotubes (SWCNT); random networks of carbon nanotubes (RN-CNTs);molecularly capped metal nanoparticles (MCNPs); metal oxidenanoparticles (MONPs); and chemically sensitive field-effect transistors(CHEM-FETs).

A system is provided herein for rapidly analyzing a vapor condensatesample using a mobile phone comprising:

-   -   (a) a device of any prior claim;    -   (b) a mobile communication device comprising:        -   i. one or a plurality of cameras for the detecting and/or            imaging the vapor condensate sample; and        -   ii. electronics, signal processors, hardware and software            for receiving and/or processing the detected signal and/or            the image of the vapor condensate sample and for remote            communication.

In some embodiments, the system further comprise a light source fromeither the mobile communication device or an external source.

In some embodiments, one of the plates has a binding site that binds ananalyte, wherein at least part of the uniform sample thickness layer isover the binding site, and is substantially less than the averagelateral linear dimension of the binding site.

In some embodiments, the system further comprising:

-   -   (d) a housing configured to hold the sample and to be mounted to        the mobile communication device.

In some embodiments, the housing comprises optics for facilitating theimaging and/or signal processing of the sample by the mobilecommunication device, and a mount configured to hold the optics on themobile communication device.

In some embodiments, an element of the optics in the housing is movablerelative to the housing.

In some embodiments, the mobile communication device is configured tocommunicate test results to a medical professional, a medical facilityor an insurance company.

In some embodiments, the mobile communication device is furtherconfigured to communicate information on the test and the subject withthe medical professional, medical facility or insurance company.

In some embodiments, the mobile communication device is furtherconfigured to communicate information of the test to a cloud network,and the cloud network process the information to refine the testresults.

In some embodiments, the mobile communication device is furtherconfigured to communicate information of the test and the subject to acloud network, the cloud network process the information to refine thetest results, and the refined test results will send back the subject.

In some embodiments, the mobile communication device is configured toreceive a prescription, diagnosis or a recommendation from a medicalprofessional.

Analysis of EBC

Breath tests are among the least invasive methods available for clinicaldiagnosis, disease state monitoring, health monitoring and environmentalexposure assessment. Exemplary methods and devices for analyzing EBC areshown in FIGS. 9-11.

EBC analysis can be used for detection of inflammatory markers, whichreflect the state of chronic airways diseases such as chronicobstructive pulmonary disease (COPD), asthma, and cystic fibrosis (CF).EBC analysis can also be used for identification of metabolic,proteomic, and genomic fingerprints of breathing, aiming for an earlydiagnosis of not only respiratory, but also systemic diseases.

A breath matrix from a subject is a mixture of nitrogen, oxygen, CO2,H2O, and inert gases. The remaining small fraction consists of more than1000 trace volatile organic compounds (VOCs) with concentrations in therange of parts per million (ppm) to parts per trillion (ppt) by volume.In terms of their origin, these volatile substances may be generated inthe body (endogenous) or may be absorbed as contaminants from theenvironment (exogenous). The composition of VOCs in breath varies widelyfrom person to person, both qualitatively and quantitatively.

Although the number of VOCs found to date in human breath is more than1000, only a few VOCs are common to all humans. These common VOCs, whichinclude isoprene, acetone, ethane, and methanol, are products of coremetabolic processes and are very informative for clinical diagnostics.The bulk matrix and trace VOCs in breath exchange between the blood andalveolar air at the blood-gas interface in the lung. One exception isNO, which is released into the airway in the case of airwayinflammation.

The endogenous compounds found in human breath, such as inorganic gases(e.g., NO and CO), VOCs (e.g., isoprene, ethane, pentane, acetone), andother typically nonvolatile substances such as isoprostanes,peroxynitrite, or cytokines, can be measured in breath condensate.Testing for endogenous compounds can provide valuable informationconcerning a possible disease state. Furthermore, exogenous molecules,particularly halogenated organic compounds, can indicate recent exposureto drugs or environmental pollutants.

Volatile Organic Compounds (VOCs) are organic substances that have ahigh vapor pressure and therefore evaporate at room temperature. TheVOCs that may be assayed as target analytes by the methods and devicesprovided by the present invention include, but not limited to,biologically generated VOCs (e.g., terpenes, isoprene, methane, greenleaf volatiles) and anthropogenic VOCs (e.g., typical solvents used inpaints and coatings, like ethyl acetate, glycol ethers, and acetone,vapors from adhesives, paints, adhesive removers, building materials,etc., like methylene chloride, MTBE, and formaldehyde, chlorofurocarbonsand perchloroethylene used in dry cleaning, vapor and exhaustive gasfrom fossil fuels, like benzene and carbon monoxide).

Detailed discussion on certain breath markers for diseases and otherhealth conditions is given in Table 1.

Besides the diseases listed in Table 1, various VOCs contained inexhaled breath have also been linked to different types of cancers. Anon-exclusive list of breath VOCs identified as biomarkers for cancersis shown in Table 2.

Besides some of the non-volatile compounds listed in Table 1, variousnon-volatile compounds have also been lined to or identified asbiomarkers of various diseases/conditions. Among these, a particularapplication of the device and method provided by the present disclosureis to assay the glucose level in EBC. Other applications include, butnot limited to, detecting the levels of nitrogen reactive species,arachidonic acid metabolites (e.g., isoprostanes, leukotrienes,prostanoids), cytokines, glutathione, proteins and metabolites, smallmolecules (e.g., chloride, sodium, potassium, urea, and small organicacids), and pH.

In some embodiments, the devices and methods of the present inventionalso find applications in the detection of drugs of abuse in EBC sample.The drugs of abuse to be detected using the devices and methods of thepresent invention include, but not limited to, ethanol, cannabis,methadone, amphetamine, methamphetamine,3,4-methylenedioxymethamphetamine, codeine, 6-acetylmorphine, diazepam,oxazepam, morphine, benzoylecgonine, cocaine, buprenorphine andtetrahydrocannabinol.

TABLE 1 Breath markers in certain diseases or conditionsDisease/Condition Breath Marker Diabetes/diabetic ketoacidosis Acetone,Ethylbenzene, Xylene, Toluene, Ethane, Pentane, Propane, Isoprene,Ethanol, Methanol, Isopropanol, 2,3,4-Trimethylhexane, 2,6,8-Trimethyldecane, Tridecane, Undecane Helicobacter pylori infectionAmmonia, volatile organic compounds Uremia/kidney failure Dimethylamine,trimethylamine Liver disease Dimethylamine, trimethylamine Liver diseaseEthanethiol, dimethylsulfide, hydrogen disulfide Liver cirrhosisAcetone, styrene, dimethylsulfide, dimethylselene Liver disease/fetorhepaticus C2-C5 Aliphatic acids, methylmercaptan Angina, ischemic heartdisease Alkanes, methylated alkanes Heart-transplant rejectionMethylated alkane contour Rheumatoid arthritis Pentane Allograftrejection CS2 Oxidative stress NO, CO, nitrosothiol, 8-isoprostane,4-hydroxy-2- nonenal, malondialdehyde, hydrogen peroxide Chronicobstructive pulmonary NO, CO, nitrosothiol, hydrogen peroxide diseaseRhinitis, rhinorrhea chronic cough NO Asthma Pentane, ethane,8-isoprostane, NO, pH, H2O2, leukotrienes (e.g., LTs, Cys-LTs, LTE4), 8-Isoprostane, PGE2, ILs, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, INF-□,RANTES, MIP□, MIP□, TNF-□, TGF- □, ET-1, Cytokeratine 1, MDA, ADMA,CCL11, hs- CRP, sICAM-1 Cystic fibrosis NO, CS2, leukotrienes (e.g.,LTE4), pH, Nitrotyrosine, Nitrites, Nitric oxide, 8-Isoprostane, IL- 6,IL-8, IL-5, TNF-□ Bronchiectasis NO Lung cancer Alkanes, monomethylatedalkanes, nitric oxide Lung carcinoma Acetone, methylethylketone,n-propanol, alkanes, aniline, o-toluidine Breast cancer 2-propanol,2,3-dihydro-1-4(1H)-quinazolinone, 1- phenyl-ethanone, heptanal,isopropyl myristate Idiopathic pulmonary fibrosis (IPF) 8-Isoprostane,H2O2, 3-nitrotyrosine, NOx, docosatetraenoyl-LPA Pulmonary arterialhypertension Natriuretic peptide, pro-BNP, ET-1, 6-keto-PGF1α, 8- (PAH)isoprostane, IL-6 Sarcoidosis 8-Isoprostane, Cys-LTs, Neopterin, TGF-□Obstructive SleepApnea Syndrome (OSA) Pediatric patients 8-Isoprostane,IL-6, LTB4, Cys-LTs, H2O2, Uric salts Adult patients 8-Isoprostane,IL-6, TNF-□, pH, H2O2, ICAM-1, IL-8 Systemic Lupus Erythematosus (SLE)IL-6, IL-8, IL-10 Chronic Renal Disease (CRD) pH, Nitrites, Nitrates,H2O2

TABLE 2 VOCs from exhaled breath that are identified in biomarkers ofvarious cancers Disease Compound name Lung cancer 1,3-Cyclopentadiene,1-methyl- 1-Cyclopentene 2,3-Butanedione 2-Butanol, 2,3-dimethyl-2-Butanone (methyl ethyl ketone) 2-Butanone, 3-hydroxy- 2-Butene,2-methyl- 3-Butyn-2-ol Acetophenone Benzaldehyde Benzene, cyclobutyl-Butane, 2-methyl- Butyl acetate Ethylenimine Isoquinoline,1,2,3,4-tetrahydro- Methyl propyl sulfide n-Pentanal n-UndecaneUndecane, 3,7-dimethyl- Urea, tetramethyl- Cyclopentane Acetone Methylethyl ketone n-Propanol 1,1′-(1-Butenylidene)bis benzene1-Methyl-4-(1-methylethyl)benzene 2,3,4-Trimethyl hexane 3,3-Dimethylpentane Dodecane 1,3-Butadiene, 2-methyl-(isoprene) 1-Heptene 1-HexeneBenzene Benzene, 1,2,4-trimethyl- Benzene, 1,4-dimethyl Benzene,1-methylethenyl- Benzene, propyl- Cyclohexane Cyclopentane, methyl-Cyclopropane, 1-methyl-2-pentyl- Decane Heptane, 2,2,4,6,6-pentamethylHeptane, 2,4-dimethyl Heptane, 2-methyl Hexanal Methane,trichlorofluoro- Nonane, 3-methyl- Octane, 3-methyl- Styrene(ethenylbenzene) Undecane Butane Decane, 5-methyl Heptane Hexane,2-methyl Hexane, 3-methyl Octane, 4-methyl Pentane Tridecane, 3-methylTridecane, 7-methyl 1,1-Biphenyl, 2,2-diethyl- 1,2-Benzenedicarboxylicacid, diethyl ester 1,5,9-Cyclododecatriene, 1,5,9-trimethyl-10,11-Dihydro-5H-dibenz[b,f]azepine 1H-Indene,2,3-dihydro-1,1,3-trimethyl-3-phenyl- 1-Propanol 2,4-Hexadiene,2,5-dimethyl- 3-Pentanone, 2,4-dimethyl- 2,5-Cyclohexadiene-1,4-dione,2,6-bis(1,1-dimethylethyl)- Benzene, 1,1-oxybis- Benzoic acid,4-ethoxy-, ethyl ester Decane, 4-methyl- Furan, 2,5-dimethyl-Pentan-1,3-dioldiisobutyrate, 2,2,4-trimethyl Propanoic acid, 2-methyl-,1-(1,1-dimethylethyl)-2-methyl-1,3- propanediyl estertrans-Caryophyllene 1,2,4,5-Tetroxane, 3,3,6,6-tetraphenyl- 1H-Indene,2,3-dihydro-4-methyl- 1-Propene, 1-(methylthio)-, (E)-2,2,4-Trimethyl-1,3-pentanediol diisobutyrate2,2,7,7-Tetramethyltricyclo-[6.2.1.0(1,6)]undec-4-en-3-one2,3-Hexanedione 2,5-Cyclohexadien-1-one,2,6-bis(1,1-dimethylethyl)-4-ethylidene 2-Methyl-3-hexanone4-Penten-2-ol 5,5-Dimethyl-1,3-hexadiene5-Isopropenyl-2-methyl-7-oxabicyclo[4.1.0]heptan-2-ol9,10-Anthracenediol, 2-ethyl- Anthracene, 1,2,3,4-tetrahydro-9-propyl-Benzene, 1,1-(1,2-cyclobutanediyl)bis,cis- Benzene,1,1-[1-(ethylthio)propylidene]bis- Benzene, 1,1-ethylidenebis, 4-ethyl-Benzophenone Bicyclo[3.2.2]nonane-1,5-dicarboxylic acid, 5-ethyl esterCamphor Ethane, 1,1,2-trichloro-1,2,2-trifluoro- Furan,2-[(2-ethoxy-3,4-dimethyl-2-cyclohexen-1-ylidene)methyl]- Isomethylionone Isopropyl alcohol Pentanoic acid,2,2,4-trimethyl-3-carboxyisopropyl, isobutyl ester Propane,2-methoxy-2-methyl- α-Isomethyl ionone Butanal Heptanal Nonanal OctanalPentanal Propanal Ethylbenzene Octane Pentamethylheptane Toluene2-Methylpentane Isoprene Xylenes total Styrene Aniline o-Toluidine1-Butanol 3-Hydroxy-2-butanone 2,6,10-T rimethyltetradecane2,6,11-Trimethyldodecane 2,6-Dimethylnaphthalene 2,6-Di-tert-butyl-,4-methylphenol 2-Methylhendecanal 2-Methylnaphthalene 2-Pentadecanone3,7-Dimethylpentadecane 3,8-Dimethylhendecane 4-Methyltetradecane5-(1-Methyl)propylnonane 5-(2-Methyl)propylnonane 5-Butylnonane5-Propyltridecane 7-Methylhexadecane 8-Hexylpentadecane8-Methylheptadecane Eicosane Hexadecanal Nonadecane NonadecanolTridecane Tridecanone Formaldehyde (methanal) Isopropanol Breast cancer2,3,4-Trimethyldecane 2-Amino-5-isopropyl-8-methyl-1-azulenecarbonitrile3,3-Dimethyl pentane 5-(2-Methylpropyl)nonane 6-Ethyl-3-octyl ester2-trifluoromethyl benzoic acid Nonane Tridecane, 5-methyl Undecane,3-methyl Pentadecane, 6-methyl Propane, 2-methyl Nonadecane, 3-methylDodecane, 4-methyl Octane, 2-methyl 1-Phenylethanone2,3-Dihydro-1-phenyl-4(1H)-quinazolinone 2-Propanol Heptanal Isopropylmyristate (+)-Longifolene 1,3-Butadiene, 2-methyl- 1,4-Pentadiene1H-Cycloprop[e]azulene, decahydro-1,1,7-trimethyl-4-methylene-1-Octanol, 2-butyl- 2,5-Cyclohexadiene-1,4-dione,2,6-bis(1,1-dimethylethyl)- 2,5-Di-tert-butyl-1,4-benzoquinone2-Hexyl-1-octanol3-Ethoxy-1,1,1,5,5,5-hexamethyl-3-(trimethylsiloxy)trisiloxane Aceticacid, 2,6,6-trimethyl-3-methylene-7-(3-oxobutylidene)oxepan-2-yl esterBenzene, 1,2,3,5-tetramethyl- Benzene, 1,2,4,5-tetramethyl- Benzene,1-ethyl-3,5-dimethyl- Benzoic acid, 4-methyl-2-trimethylsilyloxy-,trimethylsilyl ester Cyclohexene, 1-methyl-5-(1-methylethenyl)-Cyclohexene, 1-methyl-5-(1-methylethenyl)-, (R)- Cyclopropane,ethylidene Cyclotetrasiloxane, octamethyl- D-Limonene Dodecane Dodecane,2,6,11-trimethyl- Dodecane, 2,7,10-trimethyl- Longifolene-(V4)Pentadecane Tetradecane Tridecane Trifluoroacetic acid, n-octadecylester Undecane Colon cancer 1,1′-(1-Butenylidene)bis benzene1,3-Dimethylbenzene 4-(4-Propylcyclohexyl)-4′-cyano[1,1′-biphenyl]-4-ylester benzoic acid 2-Amino-5-isopropyl-8-methyl-1-azulenecarbonitrile[(1,1-Dimethylethyl)thio]acetic acid Esophagogastric Ethylphenol cancerHexanoic acid Methylphenol Phenol Gastric cancer 2-ButoxyethanolIsoprene 2-Propenenitrile 6-Methyl-5-hepten-2-one Furfural(furfuraldehyde) Head and neck 4,6-Dimethyldodecane cancer5-Methyl-3-hexanone 2,2-Dimethyldecane Limonene2,2,3-Trimethyl-exobicyclo[2.2.1]heptane 2,2-Dimethyl-propanoic acidAmmonium acetate 3-Methylhexane 2,4-Dimethylheptane 4-Methyloctanep-Xylene 2,6,6-Trimethyloctane 3-Methylnonane Liver cancer3-Hydroxy-2-butanone Styrene Decane Ovarian cancer Decanal NonanalStyrene 2-Butanone Hexadecane Prostate cancer Toluene p-Xylene2-Amino-5-isopropyl-8-methyl-1-azulenecarbonitrile 2,2-Dimethyldecane

EBC-3.2. Collection and Analysis of Other Vapor Condensates.

Certain embodiments of the present invention are related to theapplications of the SiEBCA methods and devices for collection andanalysis of the vapor condensates other than the EBC. The othermoistures include, but not limited to, fog, clouds, steams, etc. Thetarget analysis of these vapor condensates can be for different purposeenvironmental monitoring, emission control, etc. In some embodiments,the sample is a vapor from a biological sample, an environmental sample,a chemical sample, or clinical sample.

EBC-3.3. Automatic and High Throughput.

In certain embodiments, the devices and methods of the present inventionare automatic and high speed, where the steps are performed by machines.In some embodiments, the plates are in the form of roll of sheets andare controlled by rollers to put certain area of the plates into an openconfiguration or a closed configuration.

EBC-3.4. Identification and Validation of Markers in Vapor Condensate

In certain embodiments, the devices and methods of the present inventionare particularly useful for the identification and validation ofbiomarkers for human diseases/conditions, or other markers forenvironmental, food safety, or other conditions/events. Due to the ease,fast speed, small sample volume, and multiplexing potential of thepresent devices and methods, it is easy to adapt the present device forhigh-throughput and even automatic screening and validation of thesemarkers. In certain embodiments, the present devices and methods areparticularly useful when coupled with data processing system capable ofpattern recognition for such purposes.

In certain embodiments, the devices and methods of the present inventionare also advantageous to create large sample dataset for refining thealgorithms for pattern recognition through machine learning and/or othermethodologies.

EBC-4. EBC Collection and Analysis without Spacers

Another aspect of the present invention is to provide devices andmethods for collecting and analyzing vapor condensate using theaforementioned collection plate and cover plate but without spacers.

In some embodiments of the present invention, the spacers that are usedto regulate the sample or a relevant volume of the EBC sample arereplaced by (a) positioning sensors that can measure the plate innerspacing, and/or (b) devices that can control the plate positions andmove the plates into a desired plate inner spacing based on theinformation provided the sensors. In some embodiment, all the spacersare replaced by translation stage, monitoring sensors and feedbacksystem.

In some embodiments, the collection plate and the cover plate compriseno spacers at all, and the EBC sample is compressed by the two platesinto a thin layer, the thickness of which is regulated by the spacingbetween the inner surfaces of the plates (the plate spacing).

-   A4. A device for collecting EBC without spacers, comprises:

a first plate and a second plate, wherein:

-   -   i. the plates are movable relative to each other into different        configurations, and one or both plates are flexible;    -   ii. both plates comprise a sample contact area on the respective        surface of each plate for contacting EBC sample;        -   wherein one of the configurations is an open configuration,            in which: the two plates are separated apart, and the EBC            sample is deposited on one or both of the plates from a            subject; and        -   wherein another of the configurations is a closed            configuration which is configured after the EBC sample            deposition in the open configuration; and in the closed            configuration: at least part of the EBC sample is compressed            by the two plates into a thin layer, wherein the thin layer            is in contact with and confined by the inner surfaces of the            two plates.

-   A5. A method of collecting EBC without spacers, comprises the steps:    -   (a) obtaining a collection plate and a cover plate of paragraph        A4;    -   (b) depositing, when the plates are configured in the open        configuration, an EBC sample by exhaling breath from a subject        toward the collection plate, wherein the exhaled breath        condensates on a collection surface of the collection plate to        form droplets and/or puddles that have different lateral sizes        and different heights, depending upon the surface wetting        properties of the collection surface;    -   (c) after (b), bringing the cover plate over the collection        surface and then bringing the two plates into a closed        configuration by pressing the plates, wherein at the closed        configuration:        -   (i) at least a part of the EBC sample is between the cover            plate and the collection plate, and a relevant area of the            collection surface of the collection plate is covered by the            cove plate; and        -   (ii) in the relevant area, a substantial number or all of            the droplets or puddles formed in step (b) at the open            configuration merge into puddle(s) that (1) have much larger            lateral size but in a smaller number than the open            configuration and (2) touch both inner surfaces of the cover            plate and the collection plate, thereby the thickness of the            puddle(s) is confined by the inner surfaces of the plates            and equal to the spacing between the inner surfaces, and the            total surface area of the deposited EBC exposed to the            ambient is significantly reduced; and

wherein the plate spacing is the spacing between the inner surfaces ofthe cover plate and the collection plate, the relevant area is a portionor entire surface of the collection surface, and the collection surfaceis a portion or entire surface of the collection plate.

-   A6. A method of analyzing EBC without spacers, comprises the steps:    -   (a) obtaining a collection plate and a cover plate of paragraph        A4;    -   (b) depositing, when the plates are configured in the open        configuration, an EBC sample by exhaling breath from a subject        toward the collection plate, wherein the exhaled breath        condensates on a collection surface of the collection plate to        form droplets and/or puddles that have different lateral sizes        and different heights, depending upon the surface wetting        properties of the collection surface;    -   (c) after (b), bringing the cover plate over the collection        surface and then bringing the two plates into a closed        configuration by pressing the plates, wherein at the closed        configuration:        -   (i) at least a part of the EBC sample is between the cover            plate and the collection plate, and a relevant area of the            collection surface of the collection plate is covered by the            cove plate; and        -   (ii) in the relevant area, a substantial number or all of            the droplets or puddles formed in step (b) at the open            configuration merge into puddle(s) that (1) have much larger            lateral size but in a smaller number than the open            configuration and (2) touch both inner surfaces of the cover            plate and the collection plate, thereby the thickness of the            puddle(s) is confined by the inner surfaces of the plates            and equal to the spacing between the inner surfaces, and the            total surface area of the deposited EBC exposed to the            ambient is significantly reduced; and    -   (d) analyzing the EBC,

wherein the plate spacing is the spacing between the inner surfaces ofthe cover plate and the collection plate, the relevant area is a portionor entire surface of the collection surface, and the collection surfaceis a portion or entire surface of the collection plate.

In some embodiments, it is unlikely to obtain a layer of highly uniformthickness without using the spacers as discussed in the foregoingsessions. However, it is still advantageous to use the device and methodof paragraphs A4-A5 for collecting and analyzing EBC sample, for it iseasy, rapid to handle, requires no professional training and a verysmall volume of sample.

In some embodiments, the analyzing step (d) of paragraph A6 comprisesdetermining the thickness of the collected EBC sample at the closedconfiguration after the formation of the thin layer during step (c). Insome embodiments, the thickness of the collected EBC sample at theclosed configuration is equal to the spacing between the inner surfacesof the two plates.

In some embodiments, measuring the spacing between the inner surfacescomprises the use of optical interference. The optical interference canuse multiple wavelength. For example, the light signal due to theinterference of a light reflected at the inner surface of the firstplate and the second plate oscillate with the wavelength of the light.From the oscillation, one can determine the spacing between the innersurfaces. To enhance the interference signal, one of the inner surfacesor both can be coated with light reflection material.

In some embodiments, measuring the spacing between the inner surfacescomprises taking optical imaging (e.g. taking a 2D (two-dimensional)/3D(three-dimensional) image of the sample and the image taking can bemultiple times with different viewing angles, different wavelength,different phase, and/or different polarization) and image processing.

In some embodiments, the analyzing step (d) of paragraph A6 comprisesmeasuring the volume of the collected EBC sample based on the lateralarea and the thickness of the thin layer that are determined after theformation of the thin layer during step (c).

In some embodiments, measuring the entire sample area or volumecomprises taking optical imaging (e.g. taking a 2D (two-dimensional)/3D(three-dimensional) image of the sample and the image taking can bemultiple times with different viewing angles, different wavelength,different phase, and/or different polarization) and image processing.The sample lateral area means the area in the direction approximatelyparallel to the first plate and the second plate. The 3D imaging can usethe method of fringe projection profilometry (FPP), which is one of themost prevalent methods for acquiring three-dimensional (3D) images ofobjects.

In some embodiments, the measuring of the sample area or volume byimaging comprises: (a) calibration of the image scale by using a sampleof the known area or volume (e.g., The imager is a smartphone and thedimensions of the image taken by the phone can be calibrated bycomparing an image of the a sample of known dimension taken the samephone); (b) comparison of the image with the scale markers (rulers)placed on or near the first plate and second plate (discussed furtherherein), and (c) a combination of thereof.

As used herein, light may include visible light, ultraviolet light,infrared light, and/or near infrared light. Light may includewavelengths in the range from 20 nm to 20,000 nm.

In some embodiments, the pressing during step (c) of paragraphs A5-A6 isperformed by human hand.

In some embodiments, the formation and properties of the thin layer isdependent on the pressing force applied during step (c) of paragraphsA5-A6 for bringing the two plates into the closed configuration. In someembodiments, the pressing force applied during step (c) of paragraphsA5-A6 is well adjusted for forming a thin layer of EBC sample betweenthe two plates that has prerequisite parameters.

More Examples of EBC Collection and Analysis Experiments

Additional exemplary experimental testing and observation, andadditional preferred embodiments of the present invention are given.

All the exemplary experimental testing and demonstration of the presentinvention described in Section 4 (Examples) were performed under thefollowing conditions and share the following common observations.

Plates.

Only one of the two plates of SiEBCA device, termed “X-Plate”, has thespacers fixed on the sample surface of the plate, and the other plate,termed “the substrate plate”, has a planar surface and does not havespacers.

EBC Formation with No Spacers at Open and Closed Configurations

In a separate set of experiments, we tested the possibility ofcollecting EBC samples using plates with no spacers.

As presented here, the exemplary SiEBCA device also comprises acollection plate and a cover plate, while the collection plate we usedwas 25 mm×25 mm×1 mm PMMA planar plate with untreated surfaces, and thecover plate was 25 mm×25 mm×0.175 mm PMMA planar plate with bareuntreated surfaces. The EBC sample was collected by having a subjectbreathe on a collection plate for 2 sec and a cover plate wasimmediately brought to cover the collection plate and pressed against itas described above. Later, the SiEBCA together with the sample collectedtherein were subject to optical measurement and microscopy imaging.

FIG. 15 in U.S. Provisional Patent Application 62/459,972, filed on Feb.16, 2017, which is herein incorporated by reference in its entirety,schematically illustrates the optical measurement and imaging taken forthe measurement of the EBC sample thickness and lateral area,respectively. As shown in panel (A), Fabry-Pérot interferometer was usedto measure the F-P cavity resonance in the reflectance spectra at 25points on the 4×4 grid artificially generated in the center of theSiEBCA device, from which the plate spacing (and the sample thickness)is thus deduced. Each of the 25 measuring points is about 2 um by 2 umin area, and all 25 points cover an area of 20 mm by 20 mm. An averageplate spacing over the 25 points was taken as the estimate of the samplethickness (

). As shown in panel (B), a direct photo of the SiEBCA device was takento delineate the general contour of the EBC sample between the twoplates and measure the overall lateral area (S_(t)). Then microscopicimages were taken at each of the 25 points (each image covers an areaS_(i) of 1.6 mm×1.1 mm), and then these images were analyzed by an imageprocessing software to recognize and measure the total area of the airbubbles (S_(b)) in each image.

To estimate the total EBC sample lateral area, first, the percentage ofEBC liquid lateral area (a_(i)) for each measuring point is calculatedas (Si−Sb)/Si×100%; second, an average value (ã) is taken from all 25points; and finally, the total EBC sample lateral area (S_(EBC)) isestimated as S_(t)*ã.

The volume of the EBC sample (V_(EBC)) is thus determined as S_(EBC)

FIG. 16 in U.S. Provisional Patent Application 62/459,972, filed on Feb.16, 2017, which is herein incorporated by reference in its entirety,demonstrates the principle of plate spacing measurement based on F-Pcavity resonance. Panel (a) shows the schematic of F-P cavity from theSiEBCA device; panel (b) shows the typical reflectance spectrum andresonances from the device. The plate spacing (h) at each measuringpoint is calculated as:

$h = \frac{c}{2n\Delta v}$

where h is the plate spacing, c is light speed, Δv is the period infrequency domain and n is the reflective index of the EBC liquid.

As described above, the average EBC sample thickness is equal to

$\frac{\Sigma_{1}^{25}h}{25}.$

EBC sample thickness uniformity is calculated as

$\sqrt{\frac{{\Sigma_{1}^{25}\left( {h - H} \right)}^{2}}{25}}.$

FIG. 17 in U.S. Provisional Patent Application 62/459,972, filed on Feb.16, 2017, which is herein incorporated by reference in its entirety,shows microscopic images of the EBC sample collected using the exemplarySiEBCA device without spacers. Panels (a)-(b) respectively show theimages of the EBC samples at the closed configuration after handpressing the two plates with low, medium, and high pressing strength.Low strength was less than 10 kg, high strength was higher than 15 kg,and medium strength was in between the low and high strength.

Under these three different conditions, the performance of the exemplarySiEBCA device without spacers was examined and summarized in Table 3,based on the measurement and calculation methods described above. Asshown in Table 3 and FIG. 17, low strength gives thicker liquidthickness with larger bubble area, while high strength gives thinner EBCsample layer with smaller bubble area.

TABLE 3 Performance of SiEBCA without spacers Average EBC AverageCollected EBC Area EBC EBC EBC Press area S_(EBC) thickness volumethickness Strength percentage ã (mm²)

  V_(EBC) (uL) uniformity 1 Low 38% 240 1.45 0.35 58% 2 Medium 72% 4500.87 0.39 47% 3 High 98% 620 0.51 0.32 43%

-   AA0. A device for collecting and analyzing vapor condensate (VC)    sample, comprising:

a collection plate and a cover plate, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible; and    -   iii. each of the plates has, on its inner respective surface, a        sample contact area for contacting a vapor condensate (VC)        sample that contains an analyte;        -   wherein one of the configurations is an open configuration,            in which: the two plates are either completely or partially            separated apart, and the VC sample is deposited on one or            both of the plates; and        -   wherein another of the configurations is a closed            configuration which is configured after the VC sample            deposition in the open configuration; and in the closed            configuration: at least a part of the VC sample is between            the two plates and in contact with the two plates, and has a            thickness that is regulated by the two sample surfaces of            the plates and is equal to or less than 30 □m with a small            variation.

-   AA1. A device for collecting and analyzing vapor condensate (VC)    sample, comprising:

a collection plate, a cover plate, and spacers, wherein:

-   -   i. the plates are movable relative to each other into different        configurations;    -   ii. one or both plates are flexible;    -   iii. each of the plates has, on its respective inner surface, a        sample contact area for contacting a vapor condensate (VC)        sample that contains an analyte;    -   iv. the spacers are fixed to the respective inner surface of one        or both of the plates and have a predetermined substantially        uniform height and a predetermined constant inter-spacer        distance and wherein at least one of the spacers is inside the        sample contact area;    -   wherein one of the configurations is an open configuration, in        which: the two plates are either completely or partially        separated apart, the spacing between the plates is not regulated        by the spacers, and the VC sample is deposited on one or both of        the plates; and    -   wherein another of the configurations is a closed configuration        which is configured after the VC sample deposition in the open        configuration; and in the closed configuration: at least a part        of the VC sample is between the two plates and in contact with        the two plates, and has a highly uniform thickness that is        regulated by the spacers and the two sample surfaces of the        plates and is equal to or less than 30 □m with a small        variation.

-   AA2. The device of embodiment AA0 or AA1, wherein the device further    comprises a dry reagent coated on one or both of the plates.

-   AA3. The device of any prior embodiment, wherein the device further    comprises, on one or both plates, a dry binding site that has a    predetermined area, wherein the dry binding site binds to and    immobilizes an analyte in the sample.

-   AA4. The device of any prior embodiment, wherein the device further    comprises, on one or both plates, a releasable dry reagent and a    release time control material that delays the time that the    releasable dry regent is released into the sample.

-   AA5. The device of embodiment 4, wherein the release time control    material delays the time that the dry regent starts is released into    the sample by at least 3 seconds.

-   AA6. The device of any prior embodiment, wherein the device further    comprises, on one or both plates, one or a plurality of dry binding    sites and/or one or a plurality of reagent sites.

-   AA7. The device of any prior embodiment, wherein the sample is    exhale breath condensate.

-   AA8. The device of any prior embodiment, wherein the sample is a    vapor from a biological sample, an environmental sample, a chemical    sample, or clinical sample.

-   AA9. The device of any prior embodiment, wherein the analyte    comprises a molecule (e.g., a protein, peptides, DNA, RNA, nucleic    acid, or other molecules), cells, tissues, viruses, and    nanoparticles with different shapes.

-   AA10. The device of any prior embodiment, wherein the analyte    comprises volatile organic compounds (VOCs).

-   AA11. The device of any prior embodiment, wherein the analyte    comprises nitrogen, oxygen, CO2, H2O, and inert gases.

-   AA12. The device of any prior embodiment, wherein the analyte is    stained.

-   AA13. The device of any prior embodiment, wherein on one of the    sample surface, it further comprises an enclosure-spacer that    encloses a partial or entire VC samples deposited on the collection    plate.

-   AA14. The device of any prior embodiment, wherein the highly uniform    thickness has a value equal to or less than 0.5 um.

-   AA15. The device of any prior embodiment, wherein the highly uniform    thickness has a value in the range of 0.5 um to 1 um.

-   AA16. The device of any prior embodiment, wherein the highly uniform    thickness has a value in the range of 1 um to 2 um.

-   AA17. The device of any prior embodiment, wherein the highly uniform    thickness has a value in the range of 2 um to 10 um.

-   AA18. The device of any prior embodiment, wherein the highly uniform    thickness has a value in the range of 10 um to 20 um.

-   AA19. The device of any prior embodiment, wherein the highly uniform    thickness has a value in the range of 20 um to 30 um.

-   AA20. The device of any prior embodiment, wherein the thickness of    the at least a part of VC sample at the closed configuration is    larger than the thickness of VC sample deposited on the collection    plate at an open configuration.

-   AA21. The device of any prior embodiment, wherein the thickness of    the at least a part of VC sample at the closed configuration is less    than the thickness of VC sample deposited on the collection plate at    an open configuration.

-   AA22. The device of any prior device embodiment, wherein the spacers    are fixed on a plate by directly embossing the plate or injection    molding of the plate.

-   AA23. The device of any prior device embodiment, wherein the    materials of the plate and the spacers are selected from    polystyrene, PMMA, PC, COC, COP, or another plastic.

-   AA24. The device of any prior embodiment, wherein the inter-spacer    spacing is in the range of 1 um to 200 um.

-   AA25. The device of any prior embodiment, wherein the inter-spacer    spacing is in the range of 200 um to 1000 um.

-   AA26. The device of any prior embodiment, wherein the VC sample is    an exhaled breath condensate from a human or an animal.

-   AA27. The device of any prior embodiment, wherein the spacers    regulating the layer of uniform thickness have a filling factor of    at least 1%, wherein the filling factor is the ratio of the spacer    area in contact with the layer of uniform thickness to the total    plate area in contact with the layer of uniform thickness.

-   AA28. The device of any prior embodiment, wherein for spacers    regulating the layer of uniform thickness, the Young's modulus of    the spacers times the filling factor of the spacers is equal to or    larger than 10 MPa, wherein the filling factor is the ratio of the    spacer area in contact with the layer of uniform thickness to the    total plate area in contact with the layer of uniform thickness.

-   AA29. The device of any prior embodiment, wherein for a flexible    plate, the thickness of the flexible plate times the Young's modulus    of the flexible plate is in the range 60 to 750 GPa-um.

-   AA30. The device of any prior embodiment, wherein for a flexible    plate, the fourth power of the inter-spacer-distance (ISD) divided    by the thickness of the flexible plate (h) and the Young's    modulus (E) of the flexible plate, ISD4/(hE), is equal to or less    than 106 um3/GPa,

-   AA31. The device of any prior paragraph, wherein one or both plates    comprises a location marker, either on a surface of or inside the    plate, that provides information of a location of the plate.

-   AA32. The device of any prior paragraph, wherein one or both plates    comprises a scale marker, either on a surface of or inside the    plate, that provides information of a lateral dimension of a    structure of the sample and/or the plate.

-   AA33. The device of any prior embodiment, wherein one or both plates    comprises an imaging marker, either on surface of or inside the    plate, that assists an imaging of the sample.

-   AA34. The device of any prior embodiment, wherein the spacers    function as a location marker, a scale marker, an imaging marker, or    any combination of thereof.

-   AA35. The device of any prior embodiment, wherein the average    thickness of the layer of uniform thickness is about equal to a    minimum dimension of an analyte in the sample.

-   AA36. The device of any prior embodiment, wherein the inter-spacer    distance is in the range of 1 □m to 50 □m.

-   AA37. The device of any prior embodiment, wherein the inter-spacer    distance is in the range of 50 □m to 120 □m.

-   AA38. The device of any prior embodiment, wherein the inter-spacer    distance is in the range of 120 □m to 200 □m.

-   AA39. The device of any prior embodiment, wherein the inter-spacer    distance is substantially periodic.

-   AA40. The device of any prior embodiment, wherein the inter-spacer    distance is aperiodic.

-   AA41. The device of any prior embodiment, wherein the spacers are    pillars with a cross-sectional shape selected from round, polygonal,    circular, square, rectangular, oval, elliptical, or any combination    of the same.

-   AA42. The device of any prior embodiment, wherein the spacers have a    pillar shape and have a substantially flat top surface, wherein, for    each spacer, the ratio of the lateral dimension of the spacer to its    height is at least 1.

-   AA43. The device of any prior embodiment, wherein each spacer has a    ratio of the lateral dimension of the spacer to its height at least    1.

-   AA44. The device of any prior embodiment, wherein the minimum    lateral dimension of spacer is less than or substantially equal to    the minimum dimension of an analyte in the sample.

-   AA45. The device of any prior embodiment, wherein the minimum    lateral dimension of spacer is in the range of 0.5 um to 100 um.

-   AA46. The device of any prior embodiment, wherein the minimum    lateral dimension of spacer is in the range of 0.5 um to 10 um.

-   AA47. The device of any prior embodiment, wherein the spacers have a    density of at least 100/mm².

-   AA48. The device of any prior embodiment, wherein the spacers have a    density of at least 1000/mm².

-   AA49. The device of any prior embodiment, wherein at least one of    the plates is transparent.

-   AA50. The device of any prior embodiment, wherein at least one of    the plates is made from a flexible polymer.

-   AA51. The device of any prior embodiment, wherein, for a pressure    that compresses the plates, the spacers are not compressible and/or,    independently, only one of the plates is flexible.

-   AA52. The device of any of any prior embodiment, wherein the    flexible plate has a thickness in the range of 10 □m to 200 □m.

-   AA53. The device of any prior embodiment, wherein the variation is    less than 30%.

-   AA54. The device of any prior embodiment, wherein the variation is    less than 10%.

-   AA55. The device of any prior embodiment, wherein the variation is    less than 5%.

-   AA56. The device of any prior embodiment, wherein the first and    second plates are connected and are configured to be changed from    the open configuration to the closed configuration by folding the    plates.

-   AA57. The device of any prior embodiment, wherein the first and    second plates are connected by a hinge and are configured to be    changed from the open configuration to the closed configuration by    folding the plates along the hinge.

-   AA58. The device of any prior embodiment, wherein the first and    second plates are connected by a hinge that is a separate material    to the plates, and are configured to be changed from the open    configuration to the closed configuration by folding the plates    along the hinge.

-   AA59. The device of any prior embodiment, wherein the first and    second plates are made in a single piece of material and are    configured to be changed from the open configuration to the closed    configuration by folding the plates.

-   AA60. The device of any prior embodiment, wherein the layer of    uniform thickness sample is uniform over a lateral area that is at    least 100 um².

-   AA61. The device of any prior embodiment, wherein the layer of    uniform thickness sample is uniform over a lateral area that is at    least 1 mm².

-   AA62. The device of any prior embodiment, wherein the device is    configured to analyze the sample in 60 seconds or less.

-   AA63. The device of any prior embodiment, wherein at the closed    configuration, the final sample thickness device is configured to    analyze the sample in 60 seconds or less.

-   AA64. The device of any prior embodiment, wherein the device further    comprises, on one or both of the plates, one or a plurality of    amplification sites that are each capable of amplifying a signal    from the analyte or a label of the analyte when the analyte or label    is within 500 nm from an amplification site.

-   AA65. The device of any prior embodiment, wherein at the closed    configuration, the final sample thickness device is configured to    analyze the sample in 10 seconds or less.

-   AA66. The device of any prior embodiment, wherein the dry binding    site comprises a capture agent.

-   AA67. The device of any prior embodiment, wherein the dry binding    site comprises an antibody or nucleic acid.

-   AA68. The device of any prior embodiment, wherein the releasable dry    reagent is a labeled reagent.

-   AA69. The device of any prior embodiment, wherein the releasable dry    reagent is a fluorescently-labeled reagent.

-   AA70. The device of any prior embodiment, wherein the releasable dry    reagent is a fluorescently-labeled antibody.

-   AA71. The device of any prior embodiment, wherein the first plate    further comprises, on its surface, a first predetermined assay site    and a second predetermined assay site, wherein the distance between    the edges of the assay site is substantially larger than the    thickness of the uniform thickness layer when the plates are in the    closed position, wherein at least a part of the uniform thickness    layer is over the predetermined assay sites, and wherein the sample    has one or a plurality of analytes that are capable of diffusing in    the sample.

-   AA72. The device of any prior embodiment, wherein the first plate    has, on its surface, at least three analyte assay sites, and the    distance between the edges of any two neighboring assay sites is    substantially larger than the thickness of the uniform thickness    layer when the plates are in the closed position, wherein at least a    part of the uniform thickness layer is over the assay sites, and    wherein the sample has one or a plurality of analytes that are    capable of diffusing in the sample.

-   AA73. The device of any prior embodiment, wherein the first plate    has, on its surface, at least two neighboring analyte assay sites    that are not separated by a distance that is substantially larger    than the thickness of the uniform thickness layer when the plates    are in the closed position, wherein at least a part of the uniform    thickness layer is over the assay sites, and wherein the sample has    one or a plurality of analytes that are capable of diffusing in the    sample.

-   AA74. The device of any prior embodiment, wherein the releasable dry    reagent is a cell stain.

-   AA75. The device of any prior embodiment, wherein the device further    comprises a detector that is an optical detector for detecting an    optical signal.

-   AA76. The device of any prior embodiment, wherein the device further    comprises a detector that is an electrical detector for detecting an    electric signal.

-   AA77. The device of any prior embodiment, wherein the device    comprises discrete spacers that are not fixed to any of the plates,    wherein at the closed configuration, the discrete spacers are    between the inner surfaces of the two plates, and the thickness of    the sample is confined by the inner surfaces of the two plates, and    regulated by the discrete spacers and the plates.

-   AA78. The device of any prior embodiment, wherein the device further    comprises a binding site that has a chemical sensor that is made    from a material selected from the group consisting of: silicon    nanowire (Si NW; single-walled carbon nanotubes (SWCNT); random    networks of carbon nanotubes (RN-CNTs); molecularly capped metal    nanoparticles (MCNPs); metal oxide nanoparticles (MONPs); and    chemically sensitive field-effect transistors (CHEM-FETs).

-   BB1. A system for rapidly analyzing a vapor condensation sample    using a mobile phone comprising:    (a) a device of any prior AA embodiment;    (b) a mobile communication device comprising:    i. one or a plurality of cameras for the detecting and/or imaging    the vapor condensate sample; and    ii. electronics, signal processors, hardware and software for    receiving and/or processing the detected signal and/or the image of    the vapor condensate sample and for remote communication.

-   BB2. The system of any prior BB embodiment, wherein the system    further comprise a light source from either the mobile communication    device or an external source.

-   BB3. The system of any prior BB embodiment, wherein one of the    plates has a binding site that binds an analyte, wherein at least    part of the uniform sample thickness layer is over the binding site,    and is substantially less than the average lateral linear dimension    of the binding site.

-   BB4. The system of any prior BB embodiment, further comprising:    (d) a housing configured to hold the sample and to be mounted to the    mobile communication device.

-   BB5. The system of any prior BB embodiment, wherein the housing    comprises optics for facilitating the imaging and/or signal    processing of the sample by the mobile communication device, and a    mount configured to hold the optics on the mobile communication    device.

-   BB6. The system of any prior BB embodiment, wherein an element of    the optics in the housing is movable relative to the housing.

-   BB7. The system of any prior BB embodiment, wherein the mobile    communication device is configured to communicate test results to a    medical professional, a medical facility or an insurance company.

-   BB8. The system of any prior BB embodiment, wherein the mobile    communication device is further configured to communicate    information on the test and the subject with the medical    professional, medical facility or insurance company.

-   BB9. The system of any prior BB embodiment, wherein the mobile    communication device is further configured to communicate    information of the test to a cloud network, and the cloud network    process the information to refine the test results.

-   BB10. The system of any prior BB embodiment, wherein the mobile    communication device is further configured to communicate    information of the test and the subject to a cloud network, the    cloud network process the information to refine the test results,    and the refined test results will send back the subject.

-   BB11. The system of any prior BB embodiment, wherein the mobile    communication device is configured to receive a prescription,    diagnosis or a recommendation from a medical professional.

-   BB12. The system of any prior BB embodiment, wherein the mobile    communication device is configured with hardware and software to:    (a) capture an image of the sample;    (b) analyze a test location and a control location in in image; and    (c) compare a value obtained from analysis of the test location to a    threshold value that characterizes the rapid diagnostic test.

-   BB13. The system of any prior BB embodiment, wherein at least one of    the plates comprises a storage site in which assay reagents are    stored.

-   BB14. The system of any prior BB embodiment, at least one of the    cameras reads a signal from the CROF device.

-   BB15. The system of any prior BB embodiment, wherein the mobile    communication device communicates with the remote location via a    wifi or cellular network.

-   BB16. The system of any prior BB embodiment, wherein the mobile    communication device is a mobile phone.

-   CC1. A method for rapidly analyzing an analyte in a sample using a    mobile phone, comprising:    (a) depositing a sample on the device of any prior BB embodiment;    (b) assaying an analyte in the sample deposited on the device to    generate a result; and    (c) communicating the result from the mobile communication device to    a location remote from the mobile communication device.

-   CC2. The method of any prior CC embodiment, wherein the analyte    comprises a molecule (e.g., a protein, peptides, DNA, RNA, nucleic    acid, or other molecule), cells, tissues, viruses, and nanoparticles    with different shapes.

-   CC3. The method of any prior CC embodiment, wherein the analyte    comprises white blood cell, red blood cell and platelets.

-   CC4. The method of any prior CC embodiment, wherein the method    comprises:    analyzing the results at the remote location to provide an analyzed    result; and communicating the analyzed result from the remote    location to the mobile communication device.

-   CC5. The method of any prior CC embodiment, wherein the analysis is    done by a medical professional at a remote location.

-   CC6. The method of any prior CC embodiment, wherein the mobile    communication device receives a prescription, diagnosis or a    recommendation from a medical professional at a remote location.

-   CC7. The method of any prior CC embodiment, wherein the thickness of    the at least a part of VC sample at the closed configuration is    larger than the thickness of VC sample deposited on the collection    plate at an open configuration.

-   CC8. The method of any prior CC embodiment, wherein the thickness of    the at least a part of VC sample at the closed configuration is less    than the thickness of VC sample deposited on the collection plate at    an open configuration.

-   CC9. The method of any prior CC paragraph, wherein the assaying step    comprises detecting an analyte in the sample.

-   CC10. The method of any prior CC paragraph, wherein the analyte is a    biomarker.

-   CC11. The method of any prior CC embodiment, wherein the analyte is    a protein, nucleic acid, cell, or metabolite.

-   CC12. The method of any prior CC embodiment, wherein the assay done    in step (b) is a binding assay or a biochemical assay.

-   DD1. A method for analyzing an analyte in a vapor condensate sample    comprising:    obtaining a device of any prior device claim;    depositing the vapor condensate sample onto one or both pates of the    device;    placing the plates in a closed configuration and applying an    external force over at least part of the plates; and    analyzing the analytes in the layer of uniform thickness while the    plates are the closed configuration.

-   DD2. The method of any prior DD embodiment, wherein the method    comprises:

(a) obtaining a sample;

(b) obtaining a first and second plates that are movable relative toeach other into different configurations, wherein each plate has asample contact surface that is substantially planar, one or both platesare flexible, and one or both of the plates comprise spacers that arefixed with a respective sample contacting surface, and wherein thespacers have:

-   -   i. a predetermined substantially uniform height,    -   ii. a shape of pillar with substantially uniform cross-section        and a flat top surface;    -   iii. a ratio of the width to the height equal or larger than        one;    -   iv. a predetermined constant inter-spacer distance that is in        the range of 10 □m to 200 □m;    -   v. a filling factor of equal to 1% or larger;

(c) depositing the sample on one or both of the plates when the platesare configured in an open configuration, wherein the open configurationis a configuration in which the two plates are either partially orcompletely separated apart and the spacing between the plates is notregulated by the spacers;

(d), after (c), using the two plates to compress at least part of thesample into a layer of substantially uniform thickness that is confinedby the sample contact surfaces of the plates, wherein the uniformthickness of the layer is regulated by the spacers and the plates, andhas an average value equal to or less than 30 um with a variation ofless than 10%, wherein the compressing comprises:

bringing the two plates together; and

conformable pressing, either in parallel or sequentially, an area of atleast one of the plates to press the plates together to a closedconfiguration, wherein the conformable pressing generates asubstantially uniform pressure on the plates over the at least part ofthe sample, and the pressing spreads the at least part of the samplelaterally between the sample contact surfaces of the plates, and whereinthe closed configuration is a configuration in which the spacing betweenthe plates in the layer of uniform thickness region is regulated by thespacers; and

(e) analyzing the in the layer of uniform thickness while the plates arethe closed configuration;

wherein the filling factor is the ratio of the spacer contact area tothe total plate area; wherein a conformable pressing is a method thatmakes the pressure applied over an

area is substantially constant regardless the shape variation of theouter surfaces of the plates; and

wherein the parallel pressing applies the pressures on the intended areaat the same time, and a sequential pressing applies the pressure on apart of the intended area and gradually move to other area.

-   DD3. The method of any prior DD embodiment, wherein the method    comprises:    -   removing the external force after the plates are in the closed        configuration; and imaging the analytes in the layer of uniform        thickness while the plates are the closed configuration; and    -   counting a number of analytes or the labels in an area of the        image.-   DD4. The method of any prior DD embodiment, wherein the method    comprises removing the external force after the plates are in the    closed configuration; and measuring optical signal in the layer of    uniform thickness while the plates are the closed configuration.-   DD5. The method of any prior DD embodiment, wherein the inter-spacer    distance is in the range of 20 □m to 200 □m.-   DD6. The method of any prior DD embodiment, wherein the inter-spacer    distance is in the range of 5 □m to 20 □m.-   DD7. The method of any prior DD embodiment, wherein a product of the    filling factor and the Young's modulus of the spacer is 2 MPa or    larger.-   DD8. The method of any prior DD embodiment, the surface variation is    less than 50 nm.-   DD9. The method of any prior DD embodiment, further comprising a    step of calculating the concentration of an analyte in the relevant    volume of sample, wherein the calculation is based on the relevant    sample volume defined by the predetermined area of the storage site,    the uniform sample thickness at the closed configuration, and the    amount of target entity detected.-   DD10. The method of any prior DD embodiment, wherein the analyzing    step comprise counting the analyte in the sample.-   DD11. The method of any prior DD embodiment, wherein the imaging and    counting is done by:

i. illuminating the cells in the layer of uniform thickness;

ii. taking one or more images of the cells using a CCD or CMOS sensor;

iii. identifying cells in the image using a computer; and

iv. counting a number of cells in an area of the image.

-   DD12. The method of any prior DD embodiment, wherein the external    force is provided by human hand.-   DD13. The method of any prior DD embodiment, wherein it future    comprises a dry reagent coated on one or both plates.-   DD14. The method of any prior DD embodiment, wherein the layer of    uniform thickness sample has a thickness uniformity of up to +/−5%.-   DD15. The method of any prior DD embodiment, wherein the spacers are    pillars with a cross-sectional shape selected from round, polygonal,    circular, square, rectangular, oval, elliptical, or any combination    of the same.-   DD16. The method of any prior DD embodiment, wherein the spacing    between the spacers is approximately the minimum dimension of an    analyte.-   EE1. The method of any prior CC or DD embodiment, wherein one or    both plate sample contact surfaces comprises one or a plurality of    amplification sites that are each capable of amplifying a signal    from the analyte or a label of the analyte when the analyte or label    is within 500 nm from an amplification site.-   EE2. The method of any prior CC or DD embodiment, wherein the sample    is exhale breath condensate.-   EE3. The method of any prior CC or DD embodiment, wherein the sample    is a vapor from a biological sample, an environmental sample, a    chemical sample, or clinical sample.-   EE4. The method of any prior CC or DD embodiment, wherein the    analyte comprises a molecule (e.g., a protein, peptides, DNA, RNA,    nucleic acid, or other molecules), cells, tissues, viruses, and    nanoparticles with different shapes.-   EE5. The method of any prior CC or DD embodiment, wherein the    analyte comprises volatile organic compounds (VOCs).-   EE6. The method of any prior CC or DD embodiment, wherein the    analyte comprises nitrogen, oxygen, CO2, H2O, and inert gases.-   EE7. The method of any prior CC or DD embodiment, wherein the    analyte is stained.-   EE8. The method of any prior CC or DD embodiment, wherein on one of    the sample surface, it further comprises an enclosure-spacer that    encloses a partial or entire VC samples deposited on the collection    plate.-   EE9. The method of any prior CC or DD embodiment, wherein the highly    uniform thickness has a value equal to or less than 0.5 um.-   EE10. The method of any prior CC or DD embodiment, wherein the    highly uniform thickness has a value in the range of 0.5 um to 1 um.-   EE11. The method of any prior CC or DD embodiment, wherein the    highly uniform thickness has a value in the range of 1 um to 2 um.-   EE12. The method of any prior CC or DD embodiment, wherein the    highly uniform thickness has a value in the range of 2 um to 10 um.-   EE13. The method of any prior CC or DD embodiment, wherein the    highly uniform thickness has a value in the range of 10 um to 20 um.-   EE14. The method of any prior CC or DD embodiment, wherein the    highly uniform thickness has a value in the range of 20 um to 30 um.

Biomarks and Applications

Further aspects of the present disclosure include a CROF device thatincludes a plurality of capture agents that each binds to a plurality ofanalytes in a sample, i.e., a multiplexed CROF device. In suchinstances, the CROF device containing a plurality of capture agents canbe configured to detect different types of analytes (protein, nucleicacids, antibodies, etc.). The different analytes can be distinguishablefrom each other on the array based on the location within the array, theemission wavelength of the detectable label that binds to the differentanalytes, or a combination of the above.

Other pathogens that can be detected in a diagnostic sample using thedevices, systems and methods in the present invention include, but arenot limited to: Varicella zoster, Staphylococcus epidermidis,Escherichia coli, methicillin-resistant Staphylococcus aureus (MSRA),Staphylococcus aureus, Staphylococcus hominis, Enterococcus faecalis,Pseudomonas aeruginosa, Staphylococcus capitis, Staphylococcus wameri,Klebsiella pneumoniae, Haemophilus influenzae, Staphylococcus simulans,Streptococcus pneumoniae and Candida albicans; gonorrhea (Neisseriagorrhoeae), syphilis (Treponena pallidum), clamydia (Clamydatracomitis), nongonococcal urethritis (Ureaplasm urealyticum), chancroid(Haemophilus ducreyi), trichomoniasis (Trichomonas vaginalis);Pseudomonas aeruginosa, methicillin-resistant Staphlococccus aureus(MSRA), Klebsiella pneumoniae, Haemophilis influenzae, Staphylococcusaureus, Stenotrophomonas maltophilia, Haemophilis parainfluenzae,Escherichia coli, Enterococcus faecalis, Serratia marcescens,Haemophilis parahaemolyticus, Enterococcus cloacae, Candida albicans,Moraxiella catarrhalis, Streptococcus pneumoniae, Citrobacter freundii,Enterococcus faecium, Kiebsella oxytoca, Pseudomonas fluorscens,Neiseria meningitidis, Streptococcus pyogenes, Pneumocystis carinii,Kiebsella pneumoniae Legionella pneumophila, Mycoplasma pneumoniae, andMycobacterium tuberculosis, etc., as well as those listed in Tables B2and 6.

TABLE B1 Diagnostic Markers Marker disease Aβ42, amyloid beta-protein(CSF) Alzheimer's disease. fetuin-A (CSF) multiple sclerosis. tau (CSF)niemann-pick type C. secretogranin II (CSF) bipolar disorder. prionprotein (CSF) Alzheimer disease, prion disease Cytokines (CSF)HIV-associated neurocognitive disorders Alpha-synuclein (CSF)parkinsonian disorders (neuordegenerative disorders) tau protein (CSF)parkinsonian disorders neurofilament light chain (CSF) axonaldegeneration parkin (CSF) neuordegenerative disorders PTEN inducedputative kinase 1 (CSF) neuordegenerative disorders DJ-1 (CSF)neuordegenerative disorders leucine-rich repeat kinase 2 (CSF)neuordegenerative disorders mutated ATP13A2 (CSF) Kufor-Rakeb diseaseApo H (CSF) parkinson disease (PD) ceruloplasmin (CSF) PD Peroxisomeproliferator-activated receptor PD gamma coactivator-1 alpha(PGC-1α)(CSF) transthyretin (CSF) CSF rhinorrhea (nasal surgery samples)Vitamin D-binding Protein (CSF) Multiple Sclerosis Progressionproapoptotic kinase R (PKR) and its AD phosphorylated PKR (pPKR) (CSF)CXCL13 (CSF) multiple sclerosis IL-12p40, CXCL13 and IL-8 (CSF)intrathecal inflammation Dkk-3 (semen) prostate cancer p14 endocanfragment (blood) Sepsis: Endocan, specifically secreted byactivated-pulmonary vascular endothelial cells, is thought to play a keyrole in the control of the lung inflammatory reaction. Serum (blood)neuromyelitis optica ACE2 (blood) cardiovascular disease autoantibody toCD25 (blood) early diagnosis of esophageal squamous cell carcinoma hTERT(blood) lung cancer CAI25 (MUC 16) (blood) lung cancer VEGF (blood) lungcancer sIL-2 (blood) lung cancer Osteopontin (blood) lung cancer Humanepididymis protein 4 (HE4) (blood) ovarian cancer Alpha-Fetal Protein(blood) pregnancy Albumin (urine) diabetics albumin (urine) uriaalbuminuria microalbuminuria kidney leaks AFP (urine) mirror fetal AFPlevels neutrophil gelatinase-associated lipocalin Acute kidney injury(NGAL) (urine) interleukin 18 (IL-18) (urine) Acute kidney injury KidneyInjury Molecule -1 (KIM-1) (urine) Acute kidney injury Liver Fatty AcidBinding Protein (L-FABP) Acute kidney injury (urine) LMP1 (saliva)Epstein-Barr virus oncoprotein (nasopharyngeal carcinomas) BARF1(saliva) Epstein-Barr virus oncoprotein (nasopharyngeal carcinomas) IL-8(saliva) oral cancer biomarker carcinoembryonic antigen (CEA) (saliva)oral or salivary malignant tumors BRAF, CCNI, EGRF, FGF19, FRS2, GREB1,Lung cancer and LZTS1 (saliva) alpha-amylase (saliva) cardiovasculardisease carcinoembryonic antigen (saliva) Malignant tumors of the oralcavity CA 125 (saliva) Ovarian cancer IL8 (saliva) spinalcellularcarcinoma. thioredoxin (saliva) spinalcellular carcinoma. beta-2microglobulin levels - monitor activity HIV of the virus (saliva) tumornecrosis factor-alpha receptors - HIV monitor activity of the virus(saliva) CA15-3 (saliva) breast cancer

TABLE B2 Diagnostic Markers HPA axis activity (Cushing's disease, Adrenal cortex diseases, etc.): Cortisol Pregnancy/fetal development: Progesterone, human chorionic gonadotropin, Levonorgestrel, alpha-fetoprotein, early conception factor, Unconjugated Estriol, Estradiol, interleukin-6, Inhibin-A Infant development: NGAL, KIM-1, Cys-C, and B2mG, AFP, S100B, MBP Menopause: Follicle stimulating hormone (FSH), Estrogen and progesterone, testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEAS), cortisol and dehydroepiandrosterone (DHEA)  Polycystic ovary syndrome: testosterone Andropause: testosterone; testosterone precursors such as pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone (DHEA) and delta-4-androstene-3,17-dione; testosterone and dihydrotestosterone metabolites such as the 17-ketosteroids androsterone and etiocholanolone, polar metabolites in the form of diols, triols, and conjugates, as well as estradiol, estrogens, androsteindione, cortisol, FSH (follicle stimulating hormone), LH (luteinizing hormone), and GnRH (gonadotropin-releasing hormone) Coagulation status/disorders: b-Thromboglobulin, Platelet factor 4, Von Willebrand factor, Factor I: Fibrinogen, Factor II: Prothrombin, Factor III: Tissue factor, Factor IV: Calcium, Factor V: Proaccelerin, Factor VI, Factor VII: Proconvertin, Factor VIII:, Anti-hemolytic factor, Factor IX: Christmas factor, Factor X: Stuart-Prower factor, Factor XI: Plasma thromboplastin antecedent, Factor XII: Hageman factor, Factor XIII: Fibrin-stabilizing factor, Prekallikrein, High-molecular-weight kininogen, Protein C, Protein S, D-dimer, Tissue plasminogen activator, Plasminogen, a2-Antiplasmin, Plasminogen activator inhibitor 1 (PAI1) Autism: miR-484, miR-21, miR-212, miR-23a, miR-598, miR-95, miR-129, miR-431, miR-7, miR-15a, miR-27a, miR-15b, miR-148b, miR-132, or miR-128; miR-93, miR-106a, miR-539, miR-652, miR-550, miR-432, miR-193b, miR-181d, miR-146b, miR-140, miR-381, miR-320a, or miR-106b; GM1, GD1a, GD1b, or GT1b; Ceruloplasmin, Metalothioneine, Zinc, Copper, B6, B12, Glutathione, Alkaline phosphatase, and Activation of apo-alkaline phosphatases Alzheimer's Disease: miR-107, miR-29a, miR-29b-1, or miR-9; miR-128; HIF-la, BACE1, Reelin, CHRNA7, or 3Rtau/4Rtau, Reelin, Cystatin C, Truncated Cystatin C, C3a, t-Tau, Complement factor H, or alpha-2-macroglobulin; β-amyloid(1-42), β-amyloid(1-40), tau, phosphor-tau-181, acetylcholinesterase enzyme (AChE), GSK-3, PKC, VCAM-1 and ICAM-1, macrophage inflammatory proteins-1δ and -4 (MIP1δ and MIP4), regulated upon activation normal T-cell (RANTES), tumor necrosis factor-alpha (TNFα), midregional pro-atrial natriuretic peptide (MR-proANP), AD-associated neuronal thread protein (AD7c-NTP) Parkinson's Disease: miR-133b; Nurr1, BDNF, TrkB, gstml, or 5100 beta; apo-H, Ceruloplasmin, BDNF, Beta2-microglobulin, apoAll, tau, ABetal-42, DJ-1, cTnl, myoglobin, MMP-9, MMP-8, MMP-2, sICAM-1, myeloperoxidase [MPO], IL-4, and/or IL-5; B-type natiuretic peptide [BNP], IL-1α, IL-11, IL-10, TNF-α, IFN-γ, VEGF, insulin, GLP-1 (active), GLP-1 (total), TREM1, Leukotriene E4, Akt1, Aβ-40, Aβ-42, Fas ligand, PSA, G-CSF, MIP-1α, IL-22, IL-8, IL-21, IL-15, IL-6, IL-7, GM-CSF, IL-2, IL-12, IL-17α, IL-1β, MCP, IL-32 or RANTES, apolipoproteins A1, D and E, ischemia-modified albumin (IMA), fibronectin, s. alpha-amylase, aspartate aminotransferase, lactate dehydrogenase, tissue factor activity, MCP-1, sVCAM-1, sCD-40, insulin-like growth factor I (IGF-I), IGF-II Schizophrenia: miR-181b; miR-7, miR-24, miR-26b, miR-29b, miR-30b, miR-30e, miR-92, or miR-195; IFITM3, SERPINA3, GLS, or ALDH7A1BASP1; TP5B, ATP5H, ATP6V1B, DNM1, NDUFV2, NSF, PDHB Bipolar disease: FGF2, ALDH7A1, AGXT2L1, AQP4, or PCNT2 Mood disorder: Mbp, Edg2, Fgfrl, Fzd3, Mag, Pmp22, Ugt8, Erbb3, Igfbp4, Igfbp6, Pde6d, Ptprm, Nefh, Atp2c1, Atxn1, Btgl, C6orf182, Dicer1, Dnajc6, and Ednrb Major Depressive Disorder: FGFR1, FGFR2, FGFR3, or AQP4, Secretogranin, VGF, Cortisol, EGF, GCS, PPY, ACTH, AVP, CRH, MAT, A2M, ApoC3, CD4OL, IL-6, IL-13, IL-18, IL-1 ra, MPO, PAI-1, TNFA, ACRP30, ASP, FABP, INS, LEP, PRL, RETN, Testosterone, TSH, BDNF, S100B, NTF3, GDNF, ARTN Prion disease: Amyloid B4, App, IL-1R1, or SOD1; PrP(c), 14-3-3, NSE, S-100, Tau, AQP-4 Inflammation: TNF-α, IL-6, IL1β, Rheumatoid factor (RF), Antinuclear Antibody (ANA), acute phase markers including C-reactive protein (CRP), Clara Cell Protein (Uteroglobin); 14-3-3 protein epsilon; Isoform Long of Protocadherin alpha C2 precursor; Insulin-like growth factor IA precursor; Isoform 1 of Protocadherin-8 precursor; Isoform 1 of Sodium/potassium/calcium exchanger 2 precursor; Complement factor H-related 5; Di-N-acetylchitobiase precursor; Isoform 1 of Protein NDRG2; N-acetylglucosamine-6-sulfatase precursor; Isoform 1 of Semaphorin-3B precursor; Cadherin-5 precursor; UPF0454 protein Cl2orf49 precursor; Dihydrolipoyl dehydrogenase, mitochondrial precursor; Metallothionein-3; Fas apoptotic inhibitory molecule 2; Coactosin-like protein; Isoform Long of Platelet-derived growth factor A chain Precursor; Isoform Long of Endothelin-3 precursor; HLA class I histocompatibility antigen, A-1 alpha chain Precursor; Neuronal pentraxin-2 precursor; retbindin isoform 2; Neuroendocrine convertase 2 precursor; 15 kDa selenoprotein isoform 1 precursor; Phospholipase D4; Isoform 1 of CD109 antigen precursor; Ectonucleotide pyrophosphatase/phosphodiesterase family; member 6 precursor; Fascin; Golgi phosphoprotein 2; Isoform Delta 6 of Calcium/calmodulin-dependent protein kinase type II delta chain; Isoform 1 of FRAS1-related extracellular matrix protein 2 Precursor; Putative uncharacterized protein LOC130576; Isoform 1 of L-lactate dehydrogenase A chain; Isoform 1 of Polypeptide N-acetylgalactosaminyltransferase 13; Papilin; Protein DJ-1; Beta- mannosidase precursor; Protein YIPF3; Isoform 1 of Receptor-type tyrosine-protein phosphatase N2 Precursor; Cell growth regulator with EF hand domain protein 1; Sulfhydryl oxidase 2 precursor; Ig lambda chain V-II region TRO; Ig lambda chain V-VI region AR; Ig heavy chain V-III region WEA; Ig heavy chain V-III region CAM; Ig heavy chain V-III region BUR; Myosin-reactive immunoglobulin kappa chain variable region (Fragment); Microfibrillar protein 2 (Fragment); Ig kappa chain V-III region IARC/BL41 precursor; Ig kappa chain V-I region Kue; Ig kappa chain V-I region Sew; Ig kappa chain V-III region B6; IGLV6-57 protein; hypothetical protein L0C402665; Isoform 1 of Proline-rich acidic protein 1 precursor; Rheumatoid factor RF-ET13; Rheumatoid factor D5 heavy chain (Fragment); Uncharacterized protein ENSP00000375027; Uncharacterized protein ENSP00000375043; Uncharacterized protein ENSP00000375019; Isoform 1 of Protocadherin-1 precursor; Isoform 1 of Epithelial discoidin domain-containing receptor 1 precursor; Serine protease HTRA1 precursor; Isoform Delta of Poliovirus receptor-related protein 1 Precursor; chemokine (C—X—C motif) ligand 16; Plastin-2; 14-3-3 protein zeta/delta; Apolipoprotein C-I1 precursor; Brain-specific angiogenesis inhibitor 1 precursor; Semaphorin-3G precursor; Fol listatin-related protein 3 precursor; Hepatocyte growth factor activator precursor; Isoform 1 of Contactin-associated protein-like 2 precursor; Phosphoglycerate kinase 1; Gamma-enolase; Phosphoglycerate mutase 2; Low affinity immunoglobulin gamma Fc region receptor III-A precursor; Isoform Beta of Poliovirus receptor precursor; Serine protease inhibitor Kazal-type 6 precursor; Isoform 1 of Chordin precursor; Out at first protein homolog precursor; Isoform 1 of Carboxypeptidase B2 precursor; ROB02 isoform a Ig kappa chain V-III region POM; Isoform 1 of Protein-L-isoaspartate(D-aspartate) O-Methyltransferase CDNA F1145296 fis, clone BRHIP3003340, moderately similar to Actin, alpha skeletal muscle 2; Isoform 1 of RGM domain family member B precursor; Carboxypeptidase N subunit 2 precursor; Hypothetical LOC284297; L-6, IL-17, PAR-3, IL-17, T1/ST2, JunD, 5-LO, LTA4H, MBP, PLP, or alpha-beta crystalline; antithrombin III; a-2 glycoprotein 1, zinc; transthyretin (prealbumin); NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2; neurotrimin; orosomucoid 1 precursor (a- 1-acid glycoprotein-1); leucine-rich a-2-glycoprotein; leucine-rich repeat protein; α-1- antitrypsin Chronique fatigue syndrome: Cortisol; Ig alpha-1 chain C region; Polymeric immunoglobulin receptor; Protein S100-A7; Cystatin-C; Cystatin-B; 14-3-3 protein zeta/delta; Zinc-alpha-2-glycoprotein (ZAG) Sjögren's syndrome: IgA, IgG, IgM autoantibodies; IgA, lactoferrin and beta2-microglobulin; lysozyme C, and cystatin C, amylase and carbonic anhydrase; Autoantibodies (SSA/Ro; LA/SS-B) Systemic lupus erythematosus (SLE): Autoantibodies (CDC25B, APOBEC3G, ARAF, BCL2A1, CLK1, CREB1, CSNK1G1, CSNK2A1, CWC27, DLX4, DPPA2, EFHD2, EGR2, ERCC2, EWSR1, EZH2, FES, FOS, FTHL17, GEM, GNA15, GNG4, HMGB2, HNRNPUL1, HOXB6, ID2, IF135, IGF2BP3, IGHG1, JUNB, KLF6, LGALS7, LIN28A, MLLT3, NFIL3, NRBF2, PABPC1, PATZ1, PCGF2, PPP2CB, PPP3CC, PRM1, PTK2, PTPN4, PYGB, RET, RPL18A, RPS7, RRAS, SCEL, SH2B1, SMAD2, STAM, TAF9, TIE1, UBA3, VAV1, VVT1, ZAP70, ZNRD1, KIT, C6orf93, RPL34, DOM3Z, COPG2, DNCL12, RRP41, FBX09, RALBP1, PIA52, EEF1D, CONI, KATNB1, POLR2E, CCT3, KIAA0643, RPL37A, GTF2H2, MAP2K5, CDK3, RPS6KA1, MARK4, MTO1, MGC42105, NFE2L2, WDR45L, STK4, PFKFB3, NTRK3, MLF1, TRIM37, ACTL7B, RPL18A, CKS1B, TUBA1, NME6, SUCLA2, IGHG1, PRKCBP1, BAG3, TCEB3, RPL15, 55X4, MAP2K7, EEF1G, RNF38, PHLDA2, KCMF1, NUBP2, VPS45A, SSA/Ro, dsDNA, Smith, histones, thrombin) CREST syndrome: Autoantibodies (centromere) Systemic sclerosis: Autoantibodies (Type I topoisomerase) Primary biliary cirrhosis: Autoantibodies (nucleoporin 62, Sp100 nuclear antigen, nucleoporin 210kDa, mitochondria) Cirrhosis: NLT; NLT, HBsAG, AST, YKL-40, Hyaluronic acid, TIMP-1, alpha 2 macroglobulin, a-1-antitrypsin P1Z allele, haptoglobin, or acid phosphatase ACP AC Autoimmune hepatitis: Autoantibodies (Liver kidney microsomal type 1, smooth muscle) Celiac disease: Autoantibodies (tTG, actin) Celiac disease Irritable Bowel Syndrome (IBS): Anti-IgA gliadin, REG1A, MMP3 Inflammatory bowel disease (IBD): Trypsinogen IV, SERT; II-16, II-1beta, II-12, TNF-alpha, interferon gamma, II-6, Rantes, MCP-1, Resistin, or 5-HT Ulcerative colitis: IFITM1, IFITM3, STAT1, STAT3, TAP1, PSME2, PSMB8, HNF4G, KLF5, AQP8, APT2B1, SLC16A, MFAP4, CCNG2, SLC44A4, DDAH1, TOB1, 231152_at, MKNK1, CEACAM7*, 1562836_at, CDC42SE2, PSD3, 231169_at, IGL@*, GSN, GPM6B, CDV3*, PDPK1, ANP32E, ADAM9, CDH1, NLRP2, 215777_at, OSBPL1, VNN1, RABGAP1L, PHACTR2, ASH1L, 213710_s_at, CDH1, NLRP2, 215777_at, OSBPL1, VNN1, RABGAP1L, PHACTR2, ASH1, 213710_s_at, ZNF3, FUT2, IGHA1, EDEM1, GPR171, 229713_at, L00643187, FLVCR1, SNAP23*, ETNK1, L00728411, POSTN, MUC12, HOXA5, SIGLEC1, LARP5, PIGR, SPTBN1, UFM1, C6orf62, WDR90, ALDH1A3, F2RL1, IGHV1-69, DUOX2, RAB5A, or CP; (P)ASCA Hyperplastic Polyp: SLC6A14, ARHGEF10, ALS2, IL1RN, SPRy4, PTGER3, TRIM29, SERPINB5, 1560327 at, ZAK, BAG4, TRIB3, TTL, FOXQ1 Psoriasis: miR-146b, miR-20a, miR-146a, miR-31, miR-200a, miR-17-5p, miR-30e-5p, miR- 141, miR-203, miR-142-3p, miR-21, or miR-106a; miR-125b, miR-99b, miR-122a, miR-197, miR-100, miR-381, miR-518b, miR-524, let-7e, miR-30c, miR-365, miR-133b, miR-10a, miR- 133a, miR-22, miR-326, or miR-215; IL-20, VEGFR-1, VEGFR-2, VEGFR-3, or EGR1; Dermatitis herpetiformis: Autoantibodies (eTG) Miller-Fisher Syndrome: Autoantibodies (ganglioside GQ1B) Wegener's granulomatosis: Autoantibodies (c-ANCA) Neuropathies: Autoantibodies (ganglioside GD3, ganglioside GM1) Microscopic polyangiitis: Autoantibodies (p-ANCA) Polymyositis: Autoantibodies (Signal recognition particles) Scleromyositis: Autoantibodies (exosome complex Signal recognition particles) Myasthenia gravis: Autoantibodies (nicotinic acetylcholine receptor Signal recognition particles, muscle-specific kinase (MUSK) Signal recognition particles) Lambert-Eaton myasthenic syndrome: Autoantibodies (voltage-gated calcium channel (P/Q-type)) Hashimoto's thyroiditis: Autoantibodies (thyroid peroxidase) Graves' disease: Autoantibodies (TSH receptor) Paraneoplastic cerebellar syndrome: Autoantibodies (Hu, Yo (cerebellar Purkinje Cells), amphiphysin) Encephalitis: Autoantibodies (voltage-gated potassium channel (VGKC), N-methyl-D- aspartate receptor (NMDA)) Sydenham's chorea: Autoantibodies (basal ganglia neurons) Neuromyelitis: Autoantibodies (aquaporin-4) Allergies: Allergen-specific IgAs Rheumatic disease: miR-146a, miR-155, miR-132, miR-16, or miR-181; HOXD10, HOXD11, HOXD13, CCL8, LIM homeobox2, or CENP-E; TNFαRheumatoid arthritis: Autoantibodies (Rheumatoid factor, cyclic citrullinated protein), ATP- binding cassette, sub-family A, member 12 isoform b; ATP-binding cassette Al2; apolipoprotein; B-100 precursor - human; complement component 3 precursor; alpha-2- glycoprotein 1,zinc; Alpha-2-glycoprotein, zinc; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2; Protease inhibitor 1-like; protease inhibitor 1 (alpha-1-antitrypsin)-like; group-specific component (vitamin D binding protein); hDBP; serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1; Protease inhibitor (alpha-1-antitrypsin); protease inhibitor 1 (anti-elastase), alpha-1- antitrypsin; Vitronectin precursor V65 subunit; A kinase anchor protein 9 isoform 2; retrovirus- related hypothetical protein II - human retrotransposon LINE-1; nuclear receptor coactivator RAP250; peroxisome proliferator-act; nuclear receptor coactivator RAP2; Ig kappa chain NIG26 precursor ? human; Vitamin D-binding protein precursor (DBF) (Group-specific component) (GC-globulin) (VDB) complement C4A precursor [validated] Human; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1; nucleoporin 98kD isoform 4; nucleoporin 98kD; Nup98-Nup96 precursor; GLFG-repeat containing; nucleoporin; vitronectin precursor; serum spreading factor; somatomedin B; complement 5- protein; Alpha-1-antitrypsin precursor; HMG-BOX transcription; factor BBX; x 001; protein; hect domain and RLD 2; calcium channel, voltage-dependent, L type, alpha 1C subunit; Alpha-2-antiplasmin precursor (Alpha-2-plasmin inhibitor) (Alpha-2-PI) (Alpha-2-AP); Neuronal PAS domain protein 2 (Neuronal PAS2) (Member of PAS protein 4) (M0P4); Retinoic acid receptor gamma-2 (RAR-gamma-2) alpha-1-B-glycoprotein - human; Heparin cofactor II precursor (HC-II) (Protease inhibitor leuserpin 2) (HLS2); Ig gamma-1 chain C region; isocitrate dehydrogenase 3 (NAD+) alpha precursor; H-IDH alpha; isocitric dehydrogenase; isocitrate dehydrogenase [NAD] sub- unit alpha, mitochondrial; NADspecific ICDH; NAD(H)-specific isocitrate dehydrogenase alpha subunit precursor; isocitrate dehydrogenase (NAD+) alpha chain precursor; ferroxidase (EC 1.16.3.1) precursor [validated] -human; similar to zona pellucida binding protein; N-acetylneuraminic acid phosphate synthase; sialic acid synthase; sialic acid phosphate synthase; triple functional domain (PTPRF interacting); deleted in bladder cancer chromosome region candidate 1; ceruloplasmin (ferroxidase); Ceruloplasmin; RAB3A interacting protein (rabin3)-like 1; talin 2; similar to Ceruloplasmin precursor (Ferroxidase); orosomucoid 1 precursor; Orosomucoid-1 (alpha-1-acid glycoprotein-1); Ig lambda chain precursor - human; cold autoinflammatory syndrome 1; chromosome 1 open reading frame 7; angio-tensin/vasopressin receptor; similar to KIAA0913 protein; sodium channel, voltage-gated, type V, alpha polypeptide; hypothetical protein FLJ10379; orosomucoid 2; alpha-1-acid glycoprotein, type 2; Ig alpha-1 chain C region; corticosteroid binding globulin precursor; corticosteroid binding globulin; alpha-1 anti- proteinase, antitrypsin; KV3M_HUMAN IG KAPPA CHAIN V-III REGION HIC PRECURSOR; MUC_HUMAN Ig mu chain C region; similar to Ig gamma-2 chain C region; alpha-1- antichymotrypsin, precursor; alpha-1-antichymotrypsin; Antichymotrypsin; thyroid hormone receptor-associated protein, 240 kDa subunit; Ig heavy chain - human; Alpha-1- antichymotrypsin precursor (ACT) hypothetical protein XP_173158; hypothetical protein DKFZp434G2226; haptoglobin; Plasma protease C1 inhibitor precursor (C1Inh) (C1Inh) Haptoglobin-1 precursor; leucine-rich alpha-2-glycoprotein; S-arrestin; S-antigen; NAD(P)H dehydrogenase, quinone 2; NAD(P)H menadione oxidoreductase-1, di-oxin-inducible-2; NAD(P)H menadione oxi-doreductase 2, dioxin-inducible; angiotensin precursor [validated] - human; similar to KIAA1902 protein; similar to KIAA1728 protein; calpain 3 isoform d; calpain, large polypep- tide L3; calpain p94, large [catalytic] subunit; muscle-specific calcium-activated neutral protease 3 large subunit; asp (abnormal spindle)-like, microcephaly associated; haptoglobin-related protein; Haptoglobin-related locus; Ig alpha-2 chain C region; hypothetical protein DKFZp434P1818.1 - human (fragment); GC3_HUMAN Ig gamma-3 chain C region (Heavy chain disease protein) (HDC) Organ Rejection: miR-658, miR-125a, miR-320, miR-381, miR-628, miR-602, miR-629, or miR-125a; miR-324-3p, miR-611, miR-654, miR-330_MM1, miR-524, miR-17-3p_MM1, miR- 483, miR-663, miR-5,6-5p, miR-326, miR-197_MM2, or miR-346; matix metalloprotein-9, proteinase 3, or HNP Bone turnover/Osteoporosis: Pyridinoline, deoxypyridinoline, collagen type 1 corss-linked N-telopeptide (NTX), collagen type 1 corss-linked C-telopeptide (CTX), bone sialoprotein (BSP), Tartrate-resistant acid phosphatase 5b, deoxypyridinium (D-PYR) and osteocalcin (OC), hepatocyte growth factor and interleukin-1 beta, Osteocalcin, alkaline phosphatase, bone-specific alkaline phosphatase, serum type 1 procollagen (C1NP, P1NP) Jaw osteonecrosis: PTH, insulin, TNF-α, leptin, OPN, OC, OPG and IL6 Gaucher's disease: lyso-Gbl, Chitotriosidase and CCL18 Traumatic brain injury: apoA-1, S-100B, isoprostane, GFAP, NGAL, neuron-specific enolase (NSE) Septic shock: 15-Hydroxy-PG dehydrogenase (up), LAIR1 (up), NFKB1A (up), TLR2, PGLYPR1, TLR4, MD2, TLR5, IFNAR2, IRAK2, IRAK3, IRAK4, PI3K, PI3KCB, MAP2K6, MAPK14, NFKB1A, NFKB1, ILI R1, MAP2K1IP1, MKNK1, FAS, CASP4, GADD45B, SOCS3, TNFSF10, TNFSF13B, OSM, HGF, IL18R1, IL-6, Protein-C,IL-1beta Cancer: FEN-1; CEA, NSE, CA 19-9, CA 125, PSA, proGRP, SCC, NNMT, anti-p53 autoantibodies, Separase and DPPFV/Separase, SERPINA3; ACTB; AFM; AGT; AMBP; APOF; AP0A2; APOC1; APOE; APOH; SERPINC1; C1QB; C3; C4BPA; C8G; C9; SERPINA6; CD14; CP; CRP; CSK; F9; FGA; FGG; FLNA; FN1; GC; HRG; IF; IGFALS; ITGA1; ITIH1; ITIH2; ITIH4; KLKB1; LPA; MLL; MRC1; MYL2; MYO6; ORM1; SERPINF1; SERPINA1; SERPINA4; PROS1; QSCN6; RGS4; SAA4; SERPINA7; TF; TFRC; TTN; UBC; ALMS1; ATRN; PDCD11; KIAA0433; SERPINA10; BCOR; C10orf18; YY1AP1; FLJ10006; BDP1; SMARCAD1; MKL2; CHST8; MCPH1; MY018B; MICAL-L1; PGLYRP2; KCTD7; MGC27165; A1BG; A2M; ABLIM1; ACTA1; AHSG; ANK3; APCS; AP0A1; AP0A4; APOB; APOC3; APOL1; AZGP1; B2M; BF; C1R; C1S; C2; C4B; C5; C6; C7; C8A; C8B; CDK5RAP2/CDK5RA2; CHGB; CLU; COMP; CORO1A; CPN1; CUL1; DET1; DSC1; F13A1; F2; F5; FGB; GOLGA1; GSN; HBA1; HBB; HP; HPX; HSPA5; HUNK; IGFBP5; IGHG1; IGLV4-3; KIF5C; KNG1; KRT1; KRT10; KRT9; LBP; LGALS3BP; LRG1; LUM; MMP14; MYH4; NEB; NUCB2; ORM2; PF4V1; PIGR; PLG; PON1; PPBP; RBP4; RIMS1; RNF6; SAA1; SEMA3D; SERPIND1; SERPINF2; SERPING1; SF3B1; SPINK1; SPP1; SPTB; SYNE1; TAF4B; TBC1D1; TLN1; TMSB4X; TRIP11; TTR; UROC1; VTN; VWF; ZFHX2; ZYX; PSA (total prostate specific antigen), Creatinine, Prostatic acid phosphatase, PSA complexes, Prostrate-specific gene-1, CA 12-5, Carcinoembryonic Antigen (CEA), Alpha feto protein (AFP), hCG (Human chorionic gonadotropin), Inhibin, CAA Ovarian C1824, CA 27.29, CA 15-3, CAA Breast C1924, Her-2, Pancreatic, CA 19-9, CAA pancreatic, Neuron-specific enolase, Angiostatin DcR3 (Soluble decoy receptor 3), Endostatin, Ep-CAM (MK-1), Free Immunoglobulin Light Chain Kappa, Free Immunoglobulin Light Chain Lambda, Herstatin, Chromogranin A, Adrenomedullin, Integrin, Epidermal growth factor receptor, Epidermal growth factor receptor-Tyrosine kinase, Pro-adrenomedullin N-terminal 20 peptide, Vascular endothelial growth factor, Vascular endothelial growth factor receptor, Stem cell factor receptor, c-kit/KDR, KDR, and Midkine; Zinc α2-glycoprotein (ZAG) Adenoma: SI, DMBT1, CFI*, AQP1, APOD, TNFR5F17, CXCL10, CTSE, IGHA1, SLC9A3, 5LC7A1, BATF2, SOCS1, DOCK2, NOS2A, HK2, CXCL2, IL15RA, P0U2AF1, CLEC3B, ANI3BP, MGC13057, LCK*, C4BPA, HOXC6, GOLT1A, C2orf32, MORA, 240856_at, 50053, MEI53P1, HIPK1, GLS, CPLX1, 236045_x_at, GALC, AMN, CCDC69, CCL28, CPA3, TRIB2, HMGA2, PLCL2, NR3C1, ElF5A, LARP4, RP5-1022P6.2, PHLDB2, FKBP1B, INDO, CLDN8, CNTN3, PBEF1, 5LC16A9, CDC25B, TPSB2, PBEF1,1D4, GJB5, CHN2, LIMCH1, or CXCL9; ABCA8, KIAA1199, GCG, MAMDC2, C2orf32, 229670_at, IGF1, PCDH7, PRDX6, PCNA, COX2, or MUC6 Head and Neck cancer: IL-b, IL-6, IL-8, VEGF, MMP-9, TGF-β, TNF-α, MMP-7, plasminogen activated (PA), uPA, IGF, or INF-2 Barrett's esophagus: miR-21, miR-143, miR-145, miR-194, or miR-215; S100A2, 5100A4; p53, MUC1, MUC2 Lung cancer: miR-21, miR-205, miR-221 (protective), let-7a (protective), miR-137 (risky), miR-372 (risky), or miR-122a (risky); miR-17-92, miR-19a, miR-92, miR-155, miR-191, or miR-210; EGFR, PTEN, RRM1, RRM2, ABCB1, ABCG2, LRP, VEGFR2, VEGFR3, class III b-tubulin; KRAS, hENT1; RLF-MYCL1, TGF-ALK, or CD74-ROS1, CCNI, EGFR, FGF19, FRS2, and GREB1 LZTS, BRAF, FRS2, ANXA1, Haptoglobin Hp2, Zinc Alpha2-Glycoprotein, Calprotectin, Porphyromonas catoniae 16S rRNA, Campylobacter showae 16S rRNA, Streptocococcus salivaris 16S rRNA, Campylobacter rectus 16S rRNA, Veillonella parvula 16S rRNA, Kigella oralis 16S rRNA, and Granulicatella adiacens 16S rRNA Pancreatic cancer: miR-221, miR-181a, miR-155, miR-210, miR-213, miR-181b, miR-222, miR-181b-2, miR-21, miR-181b-1, miR-220, miR-181d, miR-223, miR-100-1/2, miR-125a, miR-143, miR-10a, miR-146, miR-99, miR-100, miR-199a-1, miR-10b, miR-199a-2, miR-221, miR-181a, miR-155, miR-210, miR-213, miR-181b, miR-222, miR-181b-2, miR-21, miR-181b- 1, miR-181c, miR-220, miR-181d, miR-223, miR-100-1/2, miR-125a, miR-143, miR-10a, miR- 146, miR-99, miR-100, miR-199a-1, miR-10b, miR-199a-2, miR-107, miR-103, miR-103-2, miR-125b-1, miR-205, miR-23a, miR-221, miR-424, miR-301, miR-100, miR-376a, miR-125b- 1, miR-21, miR-16-1, miR-181a, miR-181c, miR-92, miR-15, miR-155, let-7f-1, miR-212, miR- 107, miR-024-1/2, miR-18a, miR-31, miR-93, miR-224, or let-7d; miR-148a, miR-148b, miR- 375, miR-345, miR-142, miR-133a, miR-216, miR-217 or miR-139; KRAS, CTNNLB1, AKT, NCOA3, or B-RAF; BRCA2, PALB2, or p16, MBD3L2, KRAS, STIM2, DMXL2, ACRV1, DMD and CABLES1,TK2, GLTSCR2, CDKL3, TPT1 and DPM1 Breast cancer: miR-21, miR-155, miR-206, miR-122a, miR-210, miR-155, miR-206, miR- 210, or miR-21; let-7, miR-10b, miR-125a, miR-125b, miR-145, miR-143, miR-16, miR-10b, miR-125a; hsp70, MART-1, TRP, HER2, hsp70, MART-1, TRP, HER2, ER, PR, Class III b- tubulin, or VEGFA; GAS5; ETV6-NTRK3; CAH6 (Carbonic anhydrase VI), K2C4 (Cytokeratin 4), CYTA (Cystatin A), FABP4 (Epid. Fatty acid binding prot.), IGHGI (Ig gamma-1 chain C region), TRFL (Lactoferrin), BPIL1 (Bact. Perm.-increasing prot.-1), CYTC (Cystatin C), HPT (Haptoglobin), PROF1 (Profilin-1), ZA2G (Zinc-alpha-2-glycoprotein), ENOA (A1pha enolase), IGHA2 (Ig alpha-2 chain C region), IL-1 ra (Interleukin-1 receptor anatagonist protein precursor), Sl0A7 (S100 calcium-binding protein A7), and SPLC2 (Short palate, lung and nasel epith Carc. assoc. protein 2) Ovarian cancer: c-erbB-2, cancer antigen 15-3, p53, HER2/neu (c-erbB-2), 47D10 antigen, PTCD2, SLC25A20, NFKB2, RASGRP2, PDE7A, MLL, PRKCE, GPATC3, PRIC285 and GSTA4, MIPEP, PLCB2, SLC25A19, DEF6, ZNF236, Cl8orf22, COX7A2, DDX11, TOP3A, C9orf6, UFC1, PFDN2, KLRD1, LOC643641, HSP90AB1, CLCN7, TNFAIP2, PRKCE, MRPL40, FBF1, ANKRD44, CCT5, USP40, UBXD4, LRCH1, MRPL4, SCCPDH, STX6, LOC284184, FLJ23235, GPATC3, CPSF4, CREM, HIST1H1D, HPS4, FN3KRP, ANKRD16, C8 orf16, ATF71P2, PRIC285, miR-200a, miR-141, miR-200c, miR-200b, miR-21, miR-200a, miR-200b, miR-200c, miR-203, miR-205, miR-214, miR-199″, or miR-215; miR-199a, miR- 140, miR-145, miR-100, miR-let-7 cluster, or miR-125b-1; ERCC1, ER, TOPO1, TOP2A, AR, PTEN, CD24 or EGFR; VEGFA, VEGFR2, CA 125 Prostate cancer: AGPAT1, B2M, BASP2, IER3,1L1B, miR-9, miR-21, miR-141, miR-370, miR-200b, miR-210, miR-155, or miR-196a; miR-202, miR-210, miR-296, miR-320, miR-370, miR-373, miR-498, miR-503, miR-184, miR-198, miR-302c, miR-345, miR-491, miR-513, miR-32, miR-182, miR-31, miR-26a-1/2, miR-200c, miR-375, miR-196a-1/2, miR-370, miR- 425, miR-425, miR-194-1/2, miR-181a-1/2, miR-34b, let-71, miR-188, miR-25, miR-106b, miR-449, miR-99b, miR-93, miR-92-1/2, miR-125a, or miR-141; let-7a, let-7b, let-7c, let-7d, let-7g, miR-16, miR-23a, miR-23b, miR-26a, miR-92, miR-99a, miR-103, miR-125a, miR- 125b, miR-143, miR-145, miR-195, miR-199, miR-221, miR-222, miR-497, let-7f, miR-19b, miR-22, miR-26b, miR-27a, miR-27b, miR-29a, miR-29b, miR-30_5p, miR-30c, miR-100, miR-141, miR-148a, miR-205, miR-520h, miR-494, miR-490, miR-133a-1, miR-1-2, miR-218- 2, miR-220, miR-128a, miR-221, miR-499, miR-329, miR-340, miR-345, miR-410, miR-126, miR-205, miR-7-1/2, miR-145, miR-34a, miR-487, or let-7b; miR-15a, miR-16-1, miR-143 or miR-145; AR, PCA3; FASLG or TNFSF10; U50; ACSL3-ETV1, C150RF21-ETV1, FLJ35294- ETV1, HERV-ETV1, TMPRSS2-ERG, TMPRSS2-ETV1/4/5, TMPRSS2-ETV4/5, SLC5A3- ERG, SLC5A3-ETV1, SLC5A3-ETV5, KLK2-ETV4, kallikrein-2 (KLK2), C reactive protein (CRP), cysteine-rich secretory protein 3 (CRI5P3) and chromogranin A (CHGA), comprises prostatic acid phosphatase (PAP), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), PSA Esophageal Cancer: PCA3, GOLPH2, SPINK1, TMPRSS2:ERG, miR-192, miR-194, miR- 21, miR-200c, miR-93, miR-342, miR-152, miR-93, miR-25, miR-424, or miR-151; miR-27b, miR-205, miR-203, miR-342, let-7c, miR-125b, miR-100, miR-152, miR-192, miR-194, miR- 27b, miR-205, miR-203, miR-200c, miR-99a, miR-29c, miR-140, miR-103, miR-107 Gastric cancer: miR-106a, miR-21, miR-191, miR-223, miR-24-1, miR-24-2, miR-107, miR- 92-2, miR-214, miR-25, or miR-221; let-7a; RRM2, or surviving; EphA4 Gastrointestinal Stromal Tumor (GIST): DOG-1, PKC-theta, KIT, GPR20, PRKCQ, KCNK3, KCNH2, SCG2, TNFRSF6B, or CD34; PDGFRA, c-kit Colorectal carcinoma: miR-24-1, miR-29b-2, miR-20a, miR-10a, miR-32, miR-203, miR- 106a, miR-17-5p, miR-30c, miR-223, miR-126, miR-128b, miR-21, miR-24-2, miR-99b, miR- 155, miR-213, miR-150, miR-107, miR-191, miR-221, miR-20a, miR-510, miR-92, miR-513, miR-19a, miR-21, miR-20, miR-183, miR-96, miR-135b, miR-31, miR-21, miR-92, miR-222, miR-181b, miR-210, miR-20a, miR-106a, miR-93, miR-335, miR-338, miR-133b, miR-346, miR-106b, miR-153a, miR-219, miR-34a, miR-99b, miR-185, miR-223, miR-211, miR-135a, miR-127, miR-203, miR-212, miR-95, or miR-17-5p; miR-143, miR-145, miR-143, miR-126, miR-34b, miR-34c, let-7, miR-9-3, miR-34a, miR-145, miR-455, miR-484, miR-101, miR-145, miR-133b, miR-129, miR-124a, miR-30-3p, miR-328, miR-106a, miR-17-5p, miR-342, miR- 192, miR-1, miR-34b, miR-215, miR-192, miR-301, miR-324-5p, miR-30a-3p, miR-34c, miR- 331, or miR-148b; EFNB1, ERCC1, HER2, VEGF, or EGFR; AFRs, Rabs, ADAM10, CD44, NG2, ephrin-B1, MIF, b-catenin, Junction, plakoglobin, glalectin-4, RACK1, tetrspanin-8, FasL, TRAIL, A33, CEA, EGFR, dipeptidase 1, hsc-70, tetraspanins, ESCRT, TS, PTEN, or TOPO1; GREM1, DDR2, GUCY1A3, TNS1, ADAMTS1, FBLN1, FLJ38028, RDX, FAM129A, ASPN, FRMD6, MCC, RBMS1, SNA12, MEIS1, DOCK10, PLEKHC1, FAM126A, TBC1D9, VWF, DCN, ROBO1, MSRB3, LATS2, MEF2C, IGFBP3, GNB4, RCN3, AKAP12, RFTN1, 226834_at, COL5A1, GNG2, NR3C1*, SPARCL1, MAB21L2, AXIN2, 236894_at, AEBP1, AP1S2, C10orf56, LPHN2, AKT3, FRMD6, COL15A1, CRYAB, COL14A1, LOC286167, QKI, VWVTR1, GNG11, PAPPA, or ELDT1; 227458_at, INDO, CXCL9, CCR2, CD38, RARRES3, CXCL10, FAM26F, TNIP3, NOS2A, CCRL1, TLR8, IL18BP, FCRL5, SAMD9L, ECGF1, TNFSF13B, GBPS, or GBP1; TMEM37*, IL33, CA4, CCDC58, CLIC6, VERSUSNL1, ESPN, APCDD1, C13orf18, CYP4X1, ATP2A3, L00646627, MUPCDH, ANPEP, C1orf115, HSD3B2, GBA3, GABRB2, GYLTL1B, LYZ, SP025, CDKN2B, FAM89A, MOGAT2, SEMA6D, 229376_at, TSPAN5, IL6R, or SLC26A2 Melanoma: miR-19a, miR-144, miR-200c, miR-211, miR-324-5p, miR-331, or miR-374; miR- 9, miR-15a, miR-17-3p, miR-23b, miR-27a, miR-28, miR-29b, miR-30b, miR-31, miR-34b, miR-34c, miR-95, miR-96, miR-100, miR-104, miR-105, miR-106a, miR-107, miR-122a, miR- 124a, miR-125b, miR-127, miR-128a, miR-128b, miR-129, miR-135a, miR-135b, miR-137, miR-138, miR-139, miR-140, miR-141, miR-149, miR-154, miR-154#3, miR-181a, miR-182,miR-183, miR-184, miR-185, miR-189, miR-190, miR-199, miR-199b, miR-200a, miR-200b, miR-204, miR-213, miR-215, miR-216, miR-219, miR-222, miR-224, miR-299, miR-302a, miR-302b, miR-302c, miR-302d, miR-323, miR-325, let-7a, let-7b, let-7d, let-7e, or let-7g; MUM-1, beta-catenin, or Nop/5/Sik; DUSP-1, Alix, hsp70, Gib2, Gia, moesin, GAPDH, malate dehydrogenase, p120 catenin, PGRL, syntaxin-binding protein 1 & 2, septin-2, or WD-repeat containing protein 1; H/ACA (U1071), SNORA11D Head and neck cancer: miR-21, let-7, miR-18, miR-29c, miR-142-3p, miR-155, miR-146b, miR-205, or miR-21; miR-494; HPV E6, HPV E7, p53, IL-8, SAT, H3FA3; EGFR, EphB4, or EphB2; CHCHD7-PLAG1, CTNNB1-PLAG1, FHIT-HMGA2, HMGA2-NFIB, LIFR-PLAG1, or TCEA1-PLAG1 Oral squamous cell carcinoma: p53 autoantibodies, defensing-1, IncRNAs (MEG-3, MALAT-1, HOTAIR, NEAT-1, UCA) Cortisol, lactate dehydrogenase, Transferrin, cyclin D1, Maspin, alpha-amylase, IL-8, TNF-α, IL-1, IL-6, Basic fibroblast growth factor, Statherin, Cyfra 21.1, TPA, CA125, Endothelin-1, IL-β, CD44, IGF-1, MMP-2, MMP-9, CD59, Catalase, Profilin, S100A9/MRP14, M2BP, CEA, Carcinoma associated antigen CA-50, Salivary carbonyls, Maspin, 8-oxoguanine DNA glycosylase, OGG1, Phosphorylated-Src, Ki-67, Zinc finger protein 501 peptide, Hemopexin, Haptoglobin, Complement C3, Transthyretin, α1-antitrypsin, Peroxidase, GST, SOD, 8-OHdG, Glutathione, MDA, miR-125a, miR-200a, miR-31 Salivary gland tumors: Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 1 (FGFR1) Hepatocellular carcinoma: miR-221; et-7a-1, let-7a-2, let-7a-3, let-7b, let-7c, let-7d, let-7e, let-7f-2, let-fg, miR-122a, miR-124a-2, miR-130a, miR-132, miR-136, miR-141, miR-142, miR- 143, miR-145, miR-146, miR-150, miR-155(BIC), miR-181a-1, miR-181a-2, miR-181c, miR- 195, miR-199a-1-5p, miR-199a-2-5p, miR-199b, miR-200b, miR-214, miR-223, or pre-miR- 594; miR-122, miR-100, or miR-10a; miR-198 or miR-145 Renal cell carcinoma: miR-141, miR-200; miR-28, miR-185, miR-27, miR-let-7f-2; laminin receptor 1, betaig-h3, Galectin-1, a-2 Macroglobulin, Adipophilin, Angiopoietin 2, Caldesmon 1, Class 11 MHC-associated invariant chain (CD74), Collagen IV-al, Complement component, Complement component 3, Cytochrome P450, subfamily IIJ polypeptide 2, Delta sleep- inducing peptide, Fc g receptor 111a (CD16), HLA-B, HLA-DRa, HLA-DRb, HLA-SB, IFN- induced transmembrane protein 3, IFN-induced transmembrane protein 1, or Lysyl Oxidase; IF1 alpha, VEGF, PDGFRA; ALPHA-TFEB, NONO-TFE3, PRCC-TFE3, SFPQ-TFE3, CLTC- TFE3, or MALAT1-TFEBf Renal cell carcinoma: Akt, total Erk1/2, total Met, total GSK3b, total Hif1a, total p21, total AMPKa1, total VEGF, total PIGF, total VEGFR-1/Flt-1, phosphorylated Akt, phosphorylated Erk1/2, phosphorylated. Met, phosphorylated STAT3, phosphorylated GSK3b, and phosphorylated AMPKa1  Cervical cancer: HPV E6, HPV E7, or p53 Thyroid cancer: AKAP-BRAF, CCDC6-RET, ERC1-RETM, GOLGA5-RET, HOOK3-RET, HRH4-RET, KTN1-RET, NCOA4-RET, PCM1-RET, PRKARA1A-RET, RFG-RET, RFG9- RET, Ria-RET, TGF-NTRK1, TPM3-NTRK1, TPM3-TPR, TPR-MET, TPR-NTRK1, TRIM24- RET, TRIM27-RET or TRIM33-RET; PAX8-PPARy Neuroblastoma: Neuron-specific enolase (NSE)  Glioblastoma: GFAP Brain cancer: miR-21, miR-10b, miR-130a, miR-221, miR-125b-1, miR-125b-2, miR-9-2, miR-21, miR-25, or miR-123; miR-128a, miR-181c, miR-181a, or miR-181b; GOPC-ROS1; MGMT; EGFR Blood Cancers: HOX11, TALI, LY1, LM01, or LM02; TTL-ETV6, CDK6-MLL, CDK6-TLX3, ETV6-FLT3, ETV6-RUNX1, ETV6-TTL, MLL-AFF1, MLL-AFF3, MLL-AFF4, MLL-GAS7, TCBA1-ETV6, TCF3-PBX1 or TCF3-TFPT, for acute lymphocytic leukemia (ALL); BCL11B- TLX3, IL2-TNFRFS17, NUP214-ABL1, NUP98-CCDC28A, TAL1-STIL, or ETV6-ABL2, for T- cell acute lymphocytic leukemia (T-ALL); ATIC-ALK, KIAA1618-ALK, MSN-ALK, MYH9-ALK, NPM1-ALK, TGF-ALK or TPM3-ALK, for anaplastic large cell lymphoma (ALCL); BCR-ABL1, BCR-JAK2, ETV6-EVI1, ETV6-MN1 or ETV6-TCBA1, for chronic myelogenous leukemia (CML); CBFB-MYH11, CHIC2-ETV6, ETV6-ABL1, ETV6-ABL2, ETV6-ARNT, ETV6-CDX2, ETV6-HLXB9, ETV6-PER1, MEF2D-DAZAP1, AML-AFF1, MLL-ARHGAP26, MLL- ARHGEF12, MLL-CASC5, MLL-CBL, MLL-CREBBP, MLL-DAB21P, MLL-ELL, MLL-EP300, MLL-EPS15, MLL-FNBP1, MLL-FOX03A, MLL-GMPS, MLL-GPHN, MLL-MLLT1, MLL- MLLT11, MLL-MLLT3, MLL-MLLT6, MLL-MY01F, MLL-PICALM, MLL-SEPT2, MLL-SEPT6, MLL-SORBS2, MYST3-SORBS2, MYST-CREBBP, NPM1-MLF1, NUP98-HOXA13, PRDM16-EVI1, RABEP1-PDGFRB, RUNX1-EVI1, RUNX1-MDS1, RUNX1-RPL22, RUNX1- RUNX1T1, RUNX1-SH3D19, RUNX1-USP42, RUNX1-YTHDF2, RUNX1-ZNF687, or TAF15- ZNF-384, for AML; CCND1-FSTL3, for chronic lymphocytic leukemia (CLL); and FLIP1- PDGFRA, FLT3-ETV6, KIAA1509-PDGFRA, PDE4DIP-PDGFRB, NIN-PDGFRB, TP53BP1- PDGFRB, or TPM3-PDGFRB, for hyper eosinophilia/chronic eosinophilia; miR-23b, miR-24-1, miR-146, miR-155, miR-195, miR-221, miR-331, miR-29a, miR-195, miR-34a, or miR-29c; miR-15a, miR-16-1, miR-29 or miR-223; miR-128b, miR-204, miR-218, miR-331, miR-181b-1, miR-17-92 B-Cell Chronic Lymphocytic Leukemia: miR-183-prec, miR-190, miR-24-1-prec, miR-33, miR-19a, miR-140, miR-123, miR-10b, miR-15b-prec, miR-92-1, miR-188, miR-154, miR-217, miR-101, miR-141-prec, miR-153-prec, miR-196-2, miR-134, miR-141, miR-132, miR-192, or miR-181b-prec; miR-213, miR-220; ZAP70, AdipoR1; BCL3-MYC, MYC-BTG1, BCL7A-MYC, BRWD3-ARHGAP20 or BTG1-MYC B-cell lymphoma: miR-17-92 polycistron, miR-155, miR-210, or miR-21, miR-19a, miR-92, miR-142 miR-155, miR-221 miR-17-92, miR-21, miR-191, miR-205, U50; miR-17-92, miR- 155, miR-210, or miR-21; A-myb, LMO2, JNK3, CD10, bcl-6, Cyclin D2, IRF4, Flip, or CD44; CITTA-BCL6, CLTC-ALK, IL21R-BCL6, PIM1-BCL6, TFCR-BCL6, IKZF1-BCL6 or SEC31A- ALK Burkitt's lymphoma: pri-miR-155; MYC, TERT, NS, NP, MAZ, RCF3, BYSL, IDE3, CDC7, TCL1A, AUTS2, MYBL1, BMP7, ITPR3, CDC2, BACK2, TTK, MME, ALOX5, or TOP1; BCL6, KI-67; IGH-MYC, LCP1-BCL6 Endometrial cancer: miR-185, miR-106a, miR-181a, miR-210, miR-423, miR-103, miR-107, or let-7c; miR-71, miR-221, miR-193, miR-152, or miR-30c; NLRP7, AlphaV Beta6 integrin Uterine leiomyomas: let-7 family member, miR-21, miR-23b, miR-29b, or miR-197 Myelofibrosis: miR-190; miR-31, miR-150 and miR-95; miR-34a, miR-342, miR-326, miR- 105, miR-149, miR-147 Pheochromocytoma: Catecholamines (epinephrine, norepinephrine, adrenaline) Kidney disease/injury: ADBP-26, NHE3, KIM-1, glutamyltransferase, N-acetyl-beta-D- glucosaminidase, lysozyme, NGAL, L-FABP, bikunin, urea, prostaglandins, creatinine, alpha- 1-microglobulin, retinol binding protein, glutathione-S-transferases, adiponectin, beta-2- macroglobuin, calbindin-D, cysteine-rich angiogenic inducer 61, endothelial/epithial growth factors, alpha-1-acid glycoprotein (orosomucoid), prealbumin, modified albumin, albumin, transferrin, alpha-1-lipoprotein, alpha-1-antitrypsin matrix metalloproteinases (MMPs), alpha- 1-fetoprotein, Tamm Horsfall protein, homoarginine, interleukin 18, monocyte chemotactic protein-1 (MCP-1), Lipocalin, VCAN, NRP1, CCL2, CCL19, COL3A1, GZMM, alpha- galactosidase, casein kinase 2, IP-10, Mig, I-TAC, MIP-lα, MIP-3α, and MIP-1β, alpha-2- glycoprotein-Zinc, leucine-rich alpha-2-glycoprotein, uromodulin, Pacsin 2, hepcidin-20, hepcidin-25, AIF-2, urinary type-IV collagen, lipocalin-type prostaglandin D synthase (L- PGDS), urinary neutrophil gelatinase-associated lipocalin (uNGAL), Annexin Al, Rab23, Shh, Ihh, Dhh, PTCH1, PTCH2, SMO, Gli1, Gli2, Gli3, TLR4, cystatin C, AQPI, AQP2, AQP3, NKCC2, NaPill, DAHKSEVAHRFKD; [RNA:] SLC12A1, UMOD, vWF, MMPI, MMP3, SLC22A6, SLC22A 8, SLC22A 12, podocin, cubulin, LRP2, AQP9, and albumin, carcinoembryonic antigen (CEA), mucin, alpha-fetoprotein, tyrosinase, melanoma associated antigen, mutated tumor protein 53, p21, PUMA, prostate-specific antigen (PSA) or thyroglobulin, von Willebrand factor (VWF), thrombin, factor VIII, plasmin, fibrin, osteopontin (SPP1), Rab23, Shh, Ihh, Dhh, PTCH1, PTCH2, SMO, Gli1, Gli2, Gli3 Liver failure/disease: Lactoferrin, uric acid, cortisol, alpha-amylase, Carnitine; Cholic Acid; Chenodeoxycholic, Deoxycholic, Lithocholic, Glycocholic; Prostaglandin E2; 13,14-dihydro-15- keto Prostaglandin A2; Prostaglandin B2; Prostaglandin F2a; 15-keto-Prostaglandin F2a; 6- keto-Prostaglandin F1α; Thromboxane B2; 11-dehydro-Thromboxane B2; Prostaglandin D2; Prostaglandin J2; 15-deoxy-Δl2,14-Prostaglandin J2; 11β-Prostaglandin F2α; 5(S)- Hydroxyeicosatetraenoic acid; 5(S)-Hydroxyeicosapentaenoic acid; Leukotriene B4; Leukotriene B5; Leukotriene C4; Leukotriene D4; Leukotriene E4; Leukotriene F4; 12(S)- Hydroxyeicosatetraenoic acid; 12(S)-Hydroxyeicosapentaenoic acid; 15(S)- Hydroxyeicosatetraenoic acid; 15(S)-Hydroxyeicosapentaenoic acid; Lipoxin A4; 8(S)- Hydroxyeicosatetraenoic acid; 9-Hydroxyeicosatetraenoic acid; 11-Hydroxyeicosatetraenoic acid; 8-iso-Prostaglandin F2α; 9-Hydroxyoctadecadienoic acid; 13-Hydroxyoctadecadienoic acid; 20(S)-Hydroxyeicosatetraenoic acid; 9,10-Epoxyoctadecenoic acid; 12,13- Epoxyoctadecenoic acid; 12,13-Dihydroxyoctadecenoic acid; 5,6-Epoxyeicosatrienoic acid; 11,12-Epoxyeicosatrienoic acid; 14,15-Epoxyeicosatrienoic acid; 5,6-Dihydroxyeicosatrienoic acid; 8,9-Dihydroxyeicosatrienoic acid; 11,12-Dihydroxyeicosatrienoic acid; 14,15- Dihydroxyeicosatrienoic acid; 14,15-Epoxyeicosatetraenoic acid; 17,18- Epoxyeicosatetraenoic acid; 14,15-Dihydroxyeicosatetraenoic acid; 17,18- Dihydroxyeicosatetraenoic acid; 19,20-Dihydroxydocosapentaenoic acid; diacetylspermine, hemopexin, TLR4 Stroke: MMP9, S100-P, S100Al2, 5100A9, coag factor V, Arginasel, CA-IV, monocarboxylic acid transporter, ets-2, ElF2alpha, cytoskeleton associated protein 4, N-formylpeptide receptor, Ribonuclease2, N-acetylneuraminate pyruvate lyase, BCL-6, or Glycogen phosphorylase Heart failure/Cardiovascular health: 8-iso-prostaglandin F2α (8-iso-PGF2a), miR-195, miR- 208, miR-214, let-7b, let-7c, let-7e, miR-15b, miR-23a, miR-24, miR-27a, miR-27b, miR-93, miR-99b, miR-100, miR-103, miR-125b, miR-140, miR-145, miR-181a, miR-191, miR-195, miR-199a, miR-320, miR-342, miR-451, or miR-499; miR-1, miR-10a, miR-17-5p, miR-19a, miR-19b, miR-20a, miR-20b, miR-26b, miR-28, miR-30e-5p, miR-101, miR-106a, miR-126, miR-222, miR-374, miR-422b, or miR-423; MRP14, 0D69; CK-MB, cTnI (cardiac troponin), CRP, BPN, IL-6, MCSF, CD40, CD4OL, SFRP-3, NT-proBNP, troponin T, SKITHRIHWESASLL, AHKSEVAHRFK, uroguanylin, BNP, miR-378, miR-497, miR-21, miR- 99a, miR 29a, miR-30b, miR-29c, miR-331.3p, miR-19a, miR-22, miR-502.3, and miR-652; IL-16, sFas, Fas ligand, MCP-3, HGF, CTACK, EOTAXIN, adiponectin, IL-18, TIMP.4, TIMP.1, CRP, VEGF, and EGF, C-reactive protein (CRP); myoglobin (MYO), creatinine kinase myocardial band (CK-MB), cardiac troponins (cTn), and myeloperoxidase; TNF-α, and MMP-9; CD40 Vulnerable plaque: Amylase, L-6, MMP-9, PAPP-A, D-dimer, fibrinogen, Lp-PLA2, SCD40L, 11-18, oxLDL, GPx-1, MCP-1, P1GF, or CRP  High blood pressure: lysozyme Fibromyalgia: NR2D Neuropathic Pain: CCR2/4, CNP; ICAM-1, CGRP, TIMP-1, CLR-1, HSP-27, FABP, or apolipoprotein D; OX42, ED9 Tiredness/fatigue: PPGKPQGPPPQGGNQPQGPPPPPGKPQ (SEQ ID NO: 1); GNPQGPSPQGGNKPQGPPPPPGKPQ (SEQ ID NO: 2); SPPGKPQGPPQQEGNKPQGPPPPGKPQ (SEQ ID NO: 3 [[//]]); GGHPPPP (SEQ ID NO: 4), ESPSLIA (SEQ ID NO: 5); endorepellin; human herpesvirus 6, human herpesvirus 7, human cytomegalovirus, and Epstein-Barr virus (EBV) Stress: Cortisol, chromogranin A, alpha-amylase, secretary IgA, lysozyme, dehydro- androsteronesulfate; 17-ketosteroidsulfate; dehydro-epiandrostronesulfate; corticosteroid, 17- hydroxycorticosteroid, growth hormone, oxytocin, aldose reductase, apoptosis signal- regulating kinase 1, aquaporin 5, beta-endorphin, betaine GABA transporter, caspase recruitment domain protein 9, caspase 8, cyclin D, cyclooxygenase 2, cytochrome P450, cytochrome c, c-fos, c-jun, epidermal growth factor receptor, ferritin, glucocorticoid receptor, glucose regulated protein 58, glucose regulated protein 75, glutathione 5-transferase p, GroEL, heat shock protein 25/27, heat shock protein 40, heat shock protein 60, heat shock protein 70, heat shock protein 90, heat shock transcription factor-1, heme oxygenase-1, interleukin 1β, interleukin 6, interleukin 8, interleukin 10, interleukin 12, laminin, leptin receptor, matrix metalloproteinase 9, metallothionein, Mek-1, Mekk-1, inducible nitric oxide synthase, peripheral benzodiazepine receptor, p38 MAPK, salivary alpha amylase, SAPK, serotonin, serotonin receptor, substance P, superoxide dismutase Mn, superoxide dismutase Cu/Zn, superoxide dismutase EC, transforming growth factor β, tumor suppressor p53, and vasoactive intestinal peptide  Malnutrition: sIgA Nutritional status: Prealbumin, Albumin, Retinol-binding protein (RBP), Transferrin, Acylation-Stimulating Protein (ASP), Adiponectin, Agouti-Related Protein (AgRP), Angiopoietin-like Protein 4 (ANGPTL4, FIAF), C-peptide, AFABP (Adipocyte Fatty Acid Binding Protein, FABP4), Acylation-Stimulating Protein (ASP), EFABP (Epidermal Fatty Acid Binding Protein, FABP5), Glicentin, Glucagon, Glucagon-Like Peptide-1, Glucagon-Like Peptide-2, Ghrelin, Insulin, Leptin, Leptin Receptor, PYY, RELMs, Resistin, and sTfR (soluble Transferrin Receptor) Energy balance (protein excretion)/energy status/metabolic state: AMPK, pre-albumin, retinol binding protein, urea, cholesterol, lipoproteins, insulin, insulin C peptide, IGF binding proteins, e.g. IGF-BPI, liver enzymes Diabetes: 11-8, CTSS, ITGB2, HLA-DRA, CD53, PLAG27, or MMP9; RBP4; 8-iso- prostaglandin F2α (8-iso-PGF2α), 11-dehydro-thromboxane B₂ (TXM), C-peptide, Advanced glycosylation end products (AGEs), 1,5-anhydroglucitol, NGPTL3 and 4, autoantibodies (Zn transporter 8, glutamic acid decarboxylase (GAD)), ATP-binding cassette, sub-family C (CFTR/MRP), member 8; ATP-binding cassette, sub-family C (CFTR/MRP), member 9; angiotensin I converting enzyme (peptidyl-dipeptidase A) 1; adenylate cyclase activating polypeptide 1 (pituitary); adiponectin, C1Q and collagen domain containing; adiponectin receptor 1; adiponectin receptor 2; adrenomedullin; adrenergic, beta-2-, receptor, surface; advanced glycosylation end product-specific receptor; agouti related protein homolog (mouse); angiotensinogen (serpin peptidase inhibitor, clade A, member 8); angiotensin II receptor, type 1; angiotensin II receptor-associated protein; alpha-2-HS-glycoprotein; v-akt murine thymoma viral oncogene homolog 1; v-akt murine thymoma viral oncogene homolog 2; albumin; Alstrom syndrome 1; archidonate 12-lipoxygenase; ankyrin repeat domain 23; apelin, AGTRL 1 Ligand; apolipoprotein A-I; apolipoprotein A-II; apolipoprotein B (including Ag(x) antigen); apolipoprotein E; aryl hydrocarbon receptor nuclear translocator; Aryl hydrocarbon receptor nuclear translocator-like; arrestin, beta 1; arginine vasopressin (neurophysin II, antidiuretic hormone, Diabetes insipidus, neurohypophyseal); bombesin receptor subtype 3; betacellulin; benzodiazepine receptor (peripheral); complement component 3; complement component 4A (Rodgers blood group); complement component 4B (Childo blood group); complement component 5; Calpain-10; cholecystokinin; cholecystokinin (CCK)-A receptor; chemokine (C-C motif) ligand 2; CD14 molecule; CD163 molecule; CD36 molecule (thrombospondin receptor); CD38 molecule; CD3d molecule, delta (CD3-TCR complex); CD3g molecule, gamma (CD3-TCR complex); CD40 molecule, TNF receptor superfamily member 5; CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome); CD68 molecule; cyclin-dependent kinase 5; complement factor D (adipsin); CASP8 and FADD-like apoptosis regulator; Clock homolog (mouse); chymase 1, mast cell; cannabinoid receptor 1 (brain); cannabinoid receptor 2 (macrophage); cortistatin; carnitine palmitoyltransferase I; carnitine palmitoyltransferase II; complement component (3b/4b) receptor 1; complement component (3d/Epstein Barr virus) receptor 2; CREB binding protein (Rubinstein-Taybi syndrome); C-reactive protein, pentraxin-related; CREB regulated transcription coactivator 2; colony stimulating factor 1 (macrophage); cathepsin B; cathepsin L; cytochrome P450, family 19, subfamily A, polypeptide 1; Dio-2, death inducer-obliterator 1; dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2); epidermal growth factor (beta-urogastrone); early growth response 1; epididymal sperm binding protein 1; ectonucleotide; pyrophosphatase/phosphodiesterase 1; E1A binding protein p300; coagulation factor XIII, Al polypeptide; coagulation factor VIII, procoagulant component (hemophilia A); fatty acid binding protein 4, adipocyte; Fas (TNF receptor superfamily, member 6); Fas ligand (TNF superfamily, member 6); free fatty acid receptor 1; fibrinogen alpha chain; forkhead box A2; forkhead box O1A; ferritin; glutamate decarboxylase 2; galanin; gastrin; glucagon; glucokinase; gamma-glutamyltransferase 1; growth hormone 1; ghrelin/obestatin preprohormone; gastric inhibitory polypeptide; gastric inhibitory polypeptide receptor; glucagon-like peptide 1 receptor; guanine nucleotide binding protein (G protein), beta polypeptide 3; glutamic-pyruvate transaminase (alanine aminotransferase); gastrin releasing peptide (bombesin); gelsolin (amyloidosis, Finnish type); hemoglobin; hemoglobin, beta; hypocretin (orexin); neuropeptide; precursor; hepatocyte growth factor (hepapoietin A; scatter factor); hepatocyte nuclear factor 4, alpha; haptoglobin; hydroxysteroid (11-beta); dehydrogenase 1; heat shock 70 kDa protein 1B; islet amyloid polypeptide; intercellular adhesion molecule 1 (CD54), human rhinovirus receptor; interferon, gamma; insulin-like growth factor 1 (somatomedin C); insulin-like growth factor 2 (somatomedin A); insulin-like growth factor binding protein 1; insulin-like growth factor binding protein 3; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta; interleukin 10; interleukin 18 (interferon-gamma-inducing factor); interleukin 1, alpha; interleukin 1, beta; interleukin 1 receptor antagonist; interleukin 2; interleukin 6 (interferon, beta 2); interleukin 6 receptor; interleukin 8; inhibin, beta A (activin A, activin AB alpha polypeptide); insulin; insulin receptor; insulin promoter factor-1; insulin receptor substrate 1; insulin receptor substrate-2; potassium inwardly-rectifying channel, subfamily J, member 11; potassium inwardly-rectifying channel, subfamily J, member 8; klotho; kallikrein B, plasma (Fletcher factor) 1; leptin (obesity homolog, mouse); leptin receptor; legumain; lipoprotein, Lp(a); lipoprotein lipase; v-maf musculoaponeurotic brosarcoma oncogene homolog A (avian); mitogen-activated protein kinase 8; interacting protein 1; mannose-binding lectin (protein C) 2, soluble (opsonic defect); melanocortin 4 receptor; melanin-concentrating hormone receptor 1; matrix metallopeptidase 12 (macrophage elastase); matrix metallopeptidase 14 (membrane-inserted); matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase); matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa type IV collagenase); nuclear receptor co-repressor 1; neurogenic differentiation 1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(p105); nerve growth factor, beta polypeptide; non-insulin- dependent Diabetes Mellitus (common, type 2) 1; non-insulin-dependent Diabetes Mellitus (common, type 2) 2; Noninsulin-dependent Diabetes Mellitus 3; nischarin (imidazoline receptor); NF-kappaB repressing factor; neuronatin; nitric oxide synthase 2A; Niemann-Pick disease, type 02; natriuretic peptide precursor B; nuclear receptor subfamily 1, group D, member 1; nuclear respiratory factor 1; oxytocin, prepro-(neurophysin I); purinergic receptor P2Y, G-protein coupled, 10; purinergic receptor P2Y, G-protein coupled, 12; purinergic receptor P2Y, G-protein coupled, 2; progestagen-associated endometrial; protein (placental protein 14, pregnancy-associated endometrial alpha-2-globulin, alpha uterine protein); paired box gene 4; pre-B-cell colony enhancing factor 1; phosphoenolpyruvate carboxykinase 1 (PEPCK1); proprotein convertase; subtilisin/kexin type 1; placental growth factor, vascular; endothelial growth factor-related protein; phosphoinositide-3-kinase, catalytic, alpha polypeptide; phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha); phospholipase A2, group XIIA; phospholipase A2, group IID; plasminogen activator, tissue; patatin-like phospholipase domain containing 2; proopiomelanocortin (adrenocorticotropin/beta- lipotropin/alpha-melanocyte stimulating hormone/beta- melanocyte stimulating hormone/beta-endorphin); paraoxonase 1 ESA, PON, Paraoxonase; peroxisome proliferative activated receptor, alpha; peroxisome proliferative activated receptor, delta; peroxisome proliferative activated receptor, gamma; peroxisome proliferative activated receptor, gamma, coactivator 1; protein phosphatase 1, regulatory (inhibitor) subunit 3A (glycogen and sarcoplasmic reticulum binding subunit, skeletal muscle); protein phosphatase 2A, regulatory subunit B'(PR 53); protein kinase, AMP-activated, beta 1 non-catalytic subunit; protein kinase, cAMP-dependent, catalytic, alpha; protein kinase C, epsilon; proteasome (prosome, macropain) 26S subunit, non-ATPase, 9 (Bridge-1); prostaglandin E synthase; prostaglandin- endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase); protein tyrosine phosphatase, mitochondria! 1; Peptide YY retinol binding protein 4, plasma (RBP4); regenerating islet-derived 1 alpha (pancreatic stone protein, pancreatic thread protein); resistin; ribosomal protein S6 kinase, 90 kDa, polypeptide 1; Ras-related associated with Diabetes; serum amyloid Al; selectin E (endothelial adhesion molecule 1); serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6; serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1; serum/glucocorticoid regulated kinase; sex hormone-binding globulin; thioredoxin interacting protein; solute carrier family 2, member 10; solute carrier family 2, member 2; solute carrier family 2, member 4; solute carrier family 7 (cationic amino acid transporter, y+system), member 1(ERR); SNF1- like kinase 2; suppressor of cytokine signaling 3; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian); sterol regulatory element binding transcription factor 1; solute carrier family 2, member 4; somatostatin receptor 2; somatostatin receptor 5; transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1); transcription factor 2, hepatic, LF-B3, variant hepatic nuclear factor; transcription factor 7-like 2 (T-cell specific, HMG-box); transforming growth factor, beta 1 (Camurati-Engelmann disease); transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase); thrombospondin 1; thrombospondin, type I, domain containing 1; tumor necrosis factor (TNF superfamily, member 2); tumor necrosis factor (TNF superfamily, member 2); tumor necrosis factor receptor superfamily, member 1A; tumor necrosis factor receptor superfamily, member 1B; tryptophan hydroxylase 2; thyrotropin-releasing hormone; transient receptor potential cation channel, subfamily V, member 1; thioredoxin interacting protein; thioredoxin reductase 2; urocortin 3 (stresscopin); uncoupling protein 2 (mitochondria!, proton carrier); upstream transcription factor 1; urotensin 2; vascular cell adhesion molecule 1; vascular endothelial growth factor; vimentin; vasoactive intestinal peptide; vasoactive intestinal peptide receptor 1; vasoactive intestinal peptide receptor 2; von VVillebrand factor; Wolfram syndrome 1 (wolframin); X-ray repair complementing defective repair in Chinese hamster cells 6; c- peptide; cortisol; vitamin D3; estrogen; estradiol; digitalis-like factor; oxyntomodulin; dehydroepiandrosterone sulfate (DHEAS); serotonin (5-hydroxytryptamine); anti-CD38 autoantibodies; gad65 autoantibody; Angiogenin, ribonuclease, RNase A family, 5; Hemoglobin A1c; Intercellular adhesion molecule 3 (CD50); interleukin 6 signal transducer (gp130, oncostatin M receptor); selectin P (granule embrane protein 140 kDa, antigen CD62); TIMP metallopeptidase inhibitor; Proinsulin; endoglin; interleukin 2 receptor, beta; insulin-like growth factor binding protein 2; insulin-like growth factor 1 receptor; fructosamine, N-acetyl-beta-d-glucosaminidase, pentosidine, advanced glycation end product, beta2-microglobulin, pyrraline Metabolic syndrome/prediabetes: GFAP autoantibodies Alcohol abuse/dependence: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, sialic acid, β-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin; α-fucosidase (FUC), α-mannosidase (MAN), β-galactosidase (GAL), and β- glucuronidase (GLU) Non-alcoholic fatty liver disease: cytokeratin CK-18 (M65 antigen), caspase-cleaved CK-18 (M30-antigen), resistin, adiponectin, visfatin, insulin, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), or interleukin 8 (IL-8), aspartate aminotransferase (AST) and alanine aminotransferase (ALT); gamma-glutamyltransferase (GGT), immunoglobulin A, carbohydrate-deficient transferrin (CDT), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), bilirubin Cystic fibrosis: amylase, cathepsin-D, lactate dehydrogenase Ectodermal dysplasia: alpha-amylase Sarcoidosis: IL-6, TNF-α, IFN-α, IL-17, IP-10, MIG, HGF, VEGF, TNF-RII, G-CSF, IFN-γ, MCP-1, RANTES and IL-5 Asthma: eotaxin-1/CCL11, RANTES/CCL5, and IL-5; IL-1β, IL-6, MCP-1/CCL2, and IL- 8/CXCL8; IP-10/CXCL10 Periodontitis/dental caries: aspartate aminotransferase (AST) and alkaline phosphatase (ALP), uric acid and albumin; 12-HETE; MMP-8, TIMP-1, and ICTP Muscle damage: Myoglobin, creatine kinase (CK), lactate dehydrogenase (LDH), aldolase, troponin, carbonic anhydrase type 3 and fatty acid-binding protein (FABP), transaminases Infection (Mycobacterium tuberculosis): IL-32, NXNL1, PSMA7, C6orf61, EMP1, CLIC1, LACTB and DUSP3, L0C389541, MIDI IP 1, KLRC3, KLF9, FBXQ32, C50RF29, CHUK , L00652062, C6ORF60, MTMR I I, sCD170; IFN-gamma; IL-I13, IL-6, IL-8, IL-10, IL-12p70, sCD4, SCD25, SCD26, sCD32b/c, SCD50, SCD56, sCD66a, SCD83, sCD85j, SCD95, SCD106, sCD120b, sCD121b, SCD127, SCD154, SCD222, SCD226, sCDw329 and TNF alpha; VEGF, AAT, CRP, IL-IRA, TIMP-1, IL- 18, A2Macro, Haptoglobin ICAM-1, VCAM- 1, SCF, IL-17, Fibrinogen, beta-2-macroglobulin, TNF-alpha, C3 and TNFR2, GPR117, TAZ, HSDL I, HIP 1 (host)  Infection (Helicobacter pylori): MUC-5B and MUC 7 Infection (Candida species): Hsp70, calprotectin, histatins, mucins, basic proline rich proteins and peroxidases (host); Infection (influenza): Hemagglutinin (H1), neuraminidase (Ni); C-reactive protein, [RNA:] DNA cross-link repair 1A, PS02 homolog, synaptonemal complex protein 3, v-maf musculoaponeurotic fibrosarcoma oncogene family, chitinase 3-like 3, matrix metalloproteinase 12, ATP-binding cassette, sub-family E (OABP), member 1, ATP-binding cassette, sub-family F (GCN20), member 1, feminization 1 homolog a (C. elegans), general transcription factor II H. polypeptide 2, forkhead box P1, zinc finger protein 282, arginyl-tRNA synthetase-like, Mitochondrial ribosomal protein L48, ribosomal protein S4, X-linked, eukaryotic translation elongation factor 1 alpha 1, proteaseome (prosome, macropain) 28 subunit 3, GLE1 RNA export mediator-like (yeast), small nuclear ribonucleoprotein polypeptide A', cleavage and polyadenylation specific factor 2, ribosomal protein L27a, , thioredoxin domain containing 4 (endoplasmic reticulum), flap structure specific endonuclease 1, ADP-ribosylation factor-like 6 interacting protein 2, cytidine 5'-triphosphate synthase 2, glutathione S-transferase, mu 5, phospholipase D1, aspartate-beta-hydroxylase, leukotriene A4 hydrolase, cytochrome P450 family 17, subfamily a, polypeptide 1, thioredoxin interacting protein, carbonyl reductase 2, alpha globin regulatory element containing gene, male-specific lethal-2 homolog (Drosophila), RAB1, member RAS oncogene family, protein tyrosine phosphatase, non-receptor type 21, potassium voltage-gated channel, lsk-related subfamily, gene 3, BcI2-associated athanogene 3, lymphocyte cytosolic protein 2, pore forming protein- like, tumor necrosis factor receptor superfamily, member 19, filamin beta, microtubule-actin crosslinking factor 1, keratin complex 1, acidic, gene 18, keratin complex 1, acidic, gene 19, mesoderm development candiate 2, tubulin, alpha 4? glutathione peroxidase 1, integrin linked kinase, guanine nucleotide binding protein, alpha inhibiting 2, cyclin L2, tubulin, alpha 2, DEAD (Asp-Glu-Ala-Asp) box polypeptide 5, programmed cell death 4, proteasome (prosome, macropain) 26S subunit, non-ATPase 8, signal sequence receptor, beta, RAD23b homolog (host)  Infection (HIV-1): p24, gp41, gp120 Infection (Hepatitis B virus): Core, Envelope, Surface (Ay) Infection (Hepatitis C virus): Core, NS3, NS4, NS5 Infection (Hepatitis E virus): 0rf2 3 KD, 0rf2 6 KD, 0rf3 3 KD Infection (Vibrio cholerae): Cholera Toxin Infection (Corynebacterium diphtheria): Diphtheria toxin Infection (Epstein-Barr virus): EA, VCA, NA Infection (Herpes simplex virus HSV-1): gD Infection (Herpes simplex virus HSV-2): gG Infection (Clostridium tetani): Tetanus toxin Infection (Treponema pallidum): 15 kd, p47 Infection (Entamoeba histolytica): M17 Infection (Toxoplasma gondii): a2-HS glycoprotein and apB glycoprotein (host); TGME49 052280, TGME49_021500, TGME49J) 19630, TGME49_061720 and TGME49_076220 Infection (Dengue virus): IL-10, fibrinogen, C4A, immunoglobulin, tropomyosin, albumin, SCSb-9 complement complex (host); NS-1 Infection (Streptococcus pneumonia): stratifin, cullin 1, selenoprotein K, metal response element binding transcription factor 2, prostaglandin E synthase 2, HLA-B associated transcript 4, zinc finger protein (C2H2 type) 276, GCIP-interacting protein p29, mitochondrial ribosomal protein L20, aryl hydrocarbon receptor nuclear translocator-like, secretory carrier membrane protein 1, nuclear receptor subfamily 5, group A, member 2, NIMA (never in mitosis gene a)-related expressed, kinase 7, ribosomal protein L28, ribosomal protein S25, lysosomal-associated protein transmembrane 5, neural precursor cell expressed, developmentally, down-regulted gene 4, alpha glucosidase 2, alpha neutral subunit, coatomer protein complex, subunit beta 2 (beta prime), ribosomal protein L3, NADH dehydrogenase (ubiquinone) 1 alpha, subcomplex, assembly factor 1, isoprenylcysteine carboxyl methyltransferase? cytoplasmic polyadenylation element binding protein 3, mannoside acetylglucosaminyltransferase 1, RNA-binding region (RNP1, RRM) containing 1? folate receptor 4 (delta), ATPase, H+ transporting, lysosomal 50/57 kDa, V1, subunit H, zinc finger, DHHC domain containing 6, phosphoribosyl pyrophosphate synthetase-associated, protein 2, choline/ethanolaminephosphotransferase 1? solute carrier family 38, member 1, ATP synthase, H+ transporting, mitochondria! FO, complex, subunit f, isoform 2, glucose phosphate isomerase 1, 2'-5'oligoadenylate synthetase 1A, tyrosine hydroxylase, hemoglobin alpha, adult chain 1, selenoprotein P, plasma, 1, acetyl-Coenzyme A dehydrogenase, long-chain, mannosidase, beta A, lysosomal? deltex 3 homolog (Drosophila), ras homolog gene family, member AB, estrogen receptor 1 (alpha), phosphoglycerate kinase 1, , keratin complex 2, basic, gene 8, emerin, nucleoporin 153, formin 2, prothymosin alpha, synapsin l?+0cullin 4B, regulator of chromosome condensation (RCC1) and, BTB (POZ) domain containing protein 1? immediate early response 5, SAM domain and HD domain, 1, tumor rejection antigen gp96, lymphocyte antigen 6 complex, locus E, , DAZ associated protein 2, general transcription factor II I, RNA polymerase II transcriptional coactivator, SWI/SNF-related, matrix-associated actin-dependent, regulator of chromatin, subfamily a, containing DEAD/H, box 1, structure specific recognition protein 1, ankyrin repeat and FYVE domain containing 1, SET translocation, myocyte enhancer factor 2A, homeo box D9, H2A histone family, member Z, cellular nucleic acid binding protein? golgi reassembly stacking protein 2, cathepsin L, eukaryotic translation initiation factor 5, ubiquitin specific protease 9, X chromosome, proteasome (prosome, macropain) subunit, alpha type 7, pescadillo homolog 1, containing BRCT domain, (zebrafish), heterogeneous nuclear ribonucleoprotein K, DEAD (Asp-Glu-Ala-Asp) box polypeptide 52, sorting nexin 5, cathepsin B, DnaJ (Hsp40) homolog, subfamily B, member 9, ribosomal protein S3a? cytoplasmic polyadenylation element binding protein 4, 5'-3'exoribonuclease 2, small nuclear ribonucleoprotein polypeptide F, , arachidonate 5-lipoxygenase activating protein, cytochrome c oxidase, subunit Vic, RIKubiquinol cytochrome c reductase core protein 2, lactate dehydrogenase 2, B chain, ubiquinol-cytochrome c reductase core protein 1, ATP synthase, H+ transporting, mitochondria! FO, complex, subunit b, isoform 1, microsomal glutathione 5- transferase 1, ras homolog gene family, member A, RAB7, member RAS oncogene family, EGF-like module containing, mucin-like, hormone, receptor-like sequence 1, annexin A6, mitogen activated protein kinase 3, tyrosine kinase, non-receptor, 2, villin 2, tubulin, beta 5, catenin src (host); Pneumolysin, pneumococcal histidine triad D (PhtD), pneumococcal histidine triad E (PhtE), LytB, and pneumococcal choline-binding protein A (PcpA) Infection (Mycoplasma pneumonia): DnaK, L7/L12, P1, exotoxin Infection (Campylobacterjejuni): gyrA, 16S rDNA, or flaA/flaB Infection (Bacillus anthracis): Lethal factor, HtrA (BA3660), NIpC/P60-domain endopeptidase (BA1952), BA0796 locus (BA0796), SAP Infection (West Nile virus):  Infection (Human papilloma virus): E6, E7 Infection: RNase 7 (host) 

In some instances, the present method is used to inform the subject fromwhom the sample is derived about a health condition thereof. Healthconditions that may be diagnosed or measured by the present method,device and system include, but are not limited to: chemical balance;nutritional health; exercise; fatigue; sleep; stress; prediabetes;allergies; aging; exposure to environmental toxins, pesticides,herbicides, synthetic hormone analogs; pregnancy; menopause; andandropause. The following Table B3 provides a list of biomarker that canbe detected using the present invention, and their associated healthconditions.

TABLE B3 Diagnostic Markers Health Condition Source Marker DiabetesSalivapIgR, Arp 3, CA VI, and IL-1Ra; PLS-2, LEI, and IGJ chain, resistinmiscellaneousATP-binding cassette, sub-family C (CFTR/M RP), member 8; ATP-binding cassette, sub-family C (CFTR/MRP), member 9; angiotensinI converting enzyme (peptidyl-dipeptidase A) 1; adenylate cyclaseactivating polypeptide 1 (pituitary); adiponectin, C1Q and collagendomain containing; adiponectin receptor 1; adiponectin receptor 2;adrenomedullin; adrenergic, beta-2-, receptor, surface; advancedglycosylation end product-specific receptor; agouti related proteinhomolog (mouse); angiotensinogen (serpin peptidase inhibitor, cladeA, member 8); angiotensin 11 receptor, type 1; angiotensin IIreceptor-associated protein; alpha-2-HS-glycoprotein; v-akt murinethymoma viral oncogene homolog 1; v-akt murine thymoma viraloncogene homolog 2; albumin; Alstrom syndrome 1; archidonate 12-lipoxygenase; ankyrin repeat domain 23; apelin, AGTRL 1 Ligand;apolipoprotein A-I; apolipoprotein A-II; apolipoprotein B (includingAg(x) antigen); apolipoprotein E; aryl hydrocarbon receptor nucleartranslocator; Aryl hydrocarbon receptor nuclear translocator-like;arrestin, beta 1; arginine vasopressin (neurophysin II, antidiuretichormone, Diabetes insipidus, neurohypophyseal);bombesin receptor subtype 3; betacellulin; benzodiazepine receptor(peripheral); complement component 3; complement component 4A(Rodgers blood group); complement component 4B (ChiIdo bloodgroup); complement component 5; Calpain-10; cholecystokinin;cholecystokinin (CCK)-A receptor; chemokine (C-C motif) ligand 2;CD14 molecule; 0D163 molecule; 0D36 molecule (thrombospondinreceptor); 0D38 molecule; CD3d molecule, delta (CD3-TCRcomplex); CD3g molecule, gamma (CD3-TCR complex); CD40molecule, TNF receptor superfamily member 5; CD40 ligand (TNFsuperfamily, member 5, hyper-IgM syndrome); 0D68 molecule;cyclin-dependent kinase 5; complement factor D (adipsin); CASP8and FADD-like apoptosis regulator; Clock homolog (mouse);chymase 1, mast cell; cannabinoid receptor 1 (brain); cannabinoidreceptor 2 (macrophage); cortistatin; carnitine palmitoyltransferaseI; carnitine palmitoyltransferase II; complement component (3b/4b)receptor 1; complement component (3d/Epstein Barr virus) receptor2; CREB binding protein (Rubinstein-Taybi syndrome); C-reactiveprotein, pentraxin-related; CREB regulated transcription coactivator2; colony stimulating factor 1 (macrophage); cathepsin B; cathepsinL; cytochrome P450, family 19, subfamily A, polypeptide 1; Dio-2,death inducer-obliterator 1; dipeptidyl-peptidase 4 (CD26, adenosinedeaminase complexing protein 2); epidermal growth factor (beta-urogastrone); early growth response 1; epididymal sperm bindingprotein 1; ectonucleotide; pyrophosphatase/phosphodiesterase 1;ElA binding protein p300; coagulation factor XIII, Al polypeptide;coagulation factor VIII, procoagulant component (hemophilia A); fattyacid binding protein 4, adipocyte; Fas (TNF receptor superfamily,member 6); Fas ligand (TNF superfamily, member 6); free fatty acidreceptor 1; fibrinogen alpha chain; forkhead box A2; forkhead boxO1A; ferritin; glutamate decarboxylase 2; galanin; gastrin; glucagon;glucokinase; gamma-glutamyltransferase 1; growth hormone 1;ghrelin/obestatin preprohormone; gastric inhibitory polypeptide;gastric inhibitory polypeptide receptor; glucagon-like peptide 1receptor; guanine nucleotide binding protein (G protein), betapolypeptide 3; glutamic-pyruvate transaminase (alanineaminotransferase); gastrin releasing peptide (bombesin); gelsolin(amyloidosis, Finnish type); hemoglobin; hemoglobin, beta;hypocretin (orexin); neuropeptide; precursor; hepatocyte growthfactor (hepapoietin A; scatter factor); hepatocyte nuclear factor 4,alpha; haptoglobin; hydroxysteroid (11-beta); dehydrogenase 1; heatshock 70 kDa protein 1B; islet amyloid polypeptide; intercellularadhesion molecule 1 (CD54), human rhinovirus receptor; interferon,gamma; insulin-like growth factor 1 (somatomedin C); insulin-likegrowth factor 2 (somatomedin A); insulin-like growth factor bindingprotein 1; insulin-like growth factor binding protein 3; inhibitor ofkappa light polypeptide gene enhancer in B-cells, kinase beta;interleukin 10; interleukin 18 (interferon-gamma-inducing factor);interleukin 1, alpha; interleukin 1, beta; interleukin 1 receptorantagonist; interleukin 2; interleukin 6 (interferon, beta 2); interleukin6 receptor; interleukin 8; inhibin, beta A (activin A, activin AB alphapolypeptide); insulin; insulin receptor; insulin promoter factor-1;insulin receptor substrate 1; insulin receptor substrate-2; potassiuminwardly-rectifying channel, subfamily J, member 11; potassiuminwardly-rectifying channel, subfamily J, member 8; klotho; kallikreinB, plasma (Fletcher factor) 1; leptin (obesity homolog, mouse); leptinreceptor; legumain; lipoprotein, Lp(a); lipoprotein lipase; v-mafmusculoaponeurotic brosarcoma oncogene homolog A (avian);mitogen-activated protein kinase 8; interacting protein 1; mannose-binding lectin (protein C) 2, soluble (opsonic defect); melanocortin 4receptor; melanin-concentrating hormone receptor 1; matrixmetallopeptidase 12 (macrophage elastase); matrixmetallopeptidase 14 (membrane-inserted); matrix metallopeptidase2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase);matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDatype IV collagenase); nuclear receptor co-repressor 1; neurogenicdifferentiation 1; nuclear factor of kappa light polypeptide geneenhancer in B-cells 1(p105); nerve growth factor, beta polypeptide;non-insulin-dependent Diabetes Mellitus (common, type 2) 1; non-insulin-dependent Diabetes Mellitus (common, type 2) 2; Noninsulin-dependent Diabetes Mellitus 3; nischarin (imidazoline receptor); NF-kappaB repressing factor; neuronatin; nitric oxide synthase 2A;Niemann-Pick disease, type 02; natriuretic peptide precursor B;nuclear receptor subfamily 1, group D, member 1; nuclearrespiratory factor 1; oxytocin, prepro-(neurophysin I); purinergicreceptor P2Y, G-protein coupled, 10; purinergic receptor P2Y, G-protein coupled, 12; purinergic receptor P2Y, G-protein coupled, 2;progestagen-associated endometrial; protein (placental protein 14,pregnancy-associated endometrial alpha-2-globulin, alpha uterineprotein); paired box gene 4; pre-B-cell colony enhancing factor 1;phosphoenolpyruvate carboxykinase 1 (PEPCK1); proproteinconvertase; subtilisin/kexin type 1; placental growth factor, vascular;endothelial growth factor-related protein; phosphoinositide-3-kinase,catalytic, alpha polypeptide; phosphoinositide-3-kinase, regulatorysubunit 1 (p85 alpha);phospholipase A2, group XI IA; phospholipase A2, group IID;plasminogen activator, tissue; patatin-like phospholipase domaincontaining 2; proopiomelanocortin (adrenocorticotropin/beta-lipotropin/alpha-melanocyte stimulating hormone/beta- melanocytestimulating hormone/beta-endorphin); paraoxonase 1 ESA, PON,Paraoxonase; peroxisome proliferative activated receptor, alpha;peroxisome proliferative activated receptor, delta; peroxisomeproliferative activated receptor, gamma; peroxisome proliferativeactivated receptor, gamma, coactivator 1; protein phosphatase 1,regulatory(inhibitor) subunit 3A (glycogen and sarcoplasmic reticulum bindingsubunit, skeletal muscle); protein phosphatase 2A, regulatorysubunit B'(PR 53); protein kinase, AMP-activated, beta 1 non-catalytic subunit; protein kinase, cAMP-dependent, catalytic, alpha;protein kinase C, epsilon; proteasome (prosome, macropain) 26Ssubunit, non-ATPase, 9 (Bridge-1); prostaglandin E synthase;prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthaseand cyclooxygenase); protein tyrosine phosphatase, mitochondria! 1;Peptide YY retinol binding protein 4, plasma (RBP4); regeneratingislet-derived 1 alpha (pancreatic stone protein, pancreatic threadprotein); resistin; ribosomal protein S6 kinase, 90 kDa, polypeptide1; Ras-related associated with Diabetes; serum amyloid Al; selectinE (endothelial adhesion molecule 1); serpin peptidase inhibitor,clade A (alpha-1 antiproteinase, antitrypsin), member 6; serpinpeptidase inhibitor, clade E (nexin, plasminogen activator inhibitortype 1), member 1; serum/glucocorticoid regulated kinase; sexhormone-binding globulin; thioredoxin interacting protein;solute carrier family 2, member 10; solute carrier family 2, member2; solute carrier family 2, member 4; solute carrier family 7 (cationicamino acid transporter, y+30 system), member 1(ERR); SNF1-likekinase 2; suppressor of cytokine signaling 3; v-src sarcoma(Schmidt-Ruppin A-2) viral oncogene homolog (avian); sterolregulatory element binding transcription factor 1; solute carrierfamily 2, member 4; somatostatin receptor 2; somatostatin receptor5; transcription factor 1, hepatic; LF-B1, hepatic nuclear factor(HNF1); transcription factor 2, hepatic, LF-B3, variant hepaticnuclear factor; transcription factor 7-like 2 (T-cell specific, HMG-box);transforming growth factor, beta 1 (Camurati-Engelmann disease);transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase); thrombospondin 1; thrombospondin, type I,domain containing 1; tumor necrosis factor (TNF superfamily,member 2); tumor necrosis factor (TNF superfamily, member 2);tumor necrosis factor receptor superfamily, member 1A; tumornecrosis factor receptor superfamily, member 1B; tryptophanhydroxylase 2; thyrotropin-releasing hormone; transient receptorpotential cation channel, subfamily V, member 1; thioredoxininteracting protein; thioredoxin reductase 2; urocortin 3 (stresscopin);uncoupling protein 2 (mitochondria!, proton carrier); upstreamtranscription factor 1; urotensin 2; vascular cell adhesion molecule 1;vascular endothelial growth factor; vimentin; vasoactive intestinalpeptide; vasoactive intestinal peptide receptor 1; vasoactiveintestinal peptide receptor 2; von VVillebrand factor; Wolframsyndrome 1 (wolframin); X-ray repair complementing defective repairin Chinese hamster cells 6; c-peptide; cortisol; vitamin D3; estrogen;estradiol; digitalis-like factor; oxyntomodulin;dehydroepiandrosterone sulfate (DHEAS); serotonin (5-hydroxytryptamine); anti-CD38 autoantibodies; gad65 autoantibody;Angiogenin, ribonuclease, RNase A family, 5; Hemoglobin A1c;Intercellular adhesion molecule 3 (CD50); interleukin 6 signaltransducer (gp130, oncostatin M receptor); selectin P (granuleembrane protein 140 kDa, antigen CD62); TIMP metallopeptidaseinhibitor; Proinsulin; endoglin;interleukin 2 receptor, beta; insulin-like growth factor bindingprotein 2; insulin-like growth factor 1 receptor; fructosamine, N-acetyl-beta-d-glucosaminidase, pentosidine, advanced glycation endproduct, beta2-microglobulin, pyrraline Metabolic SerumGFAP autoantibodies syndrome/ prediabetes Kidney salivaLactoferrin, uric acid, cortisol, alpha-amylase failure/ miscellaneousADBP-26, NHE3, KIM-1, glutamyltransferase, N-acetyl-beta-D- diseaseglucosaminidase, lysozyme, NGAL, L-FABP, bikunin, urea,prostaglandins, creatinine, alpha-1-microglobulin, retinol bindingprotein, glutathione-S-transferases, adiponectin, beta-2-macroglobuin, calbindin-D, cysteine-rich angiogenic inducer 61,endothelial/epithial growth factors, alpha-1-acid glycoprotein(orosomucoid), prealbumin, modified albumin, albumin, transferrin,alpha-1-lipoprotein, alpha-1-antitrypsin matrix metalloproteinases(MMPs), alpha-1-fetoprotein, Tamm Horsfall protein, homoarginine,interleukin 18, monocyte chemotactic protein-1 (MCP-1), Lipocalin,VCAN, NRP1, CCL2, CCL19, COL3A1, GZMM, alpha-galactosidase, casein kinase 2, IP-10, Mig, I-TAC, MIP-1 a, MIP-3a,and MIP-113, alpha-2-glycoprotein-Zinc, leucine-rich alpha-2-glycoprotein, uromodulin, Pacsin 2, hepcidin-20, hepcidin-25, AIF-2,urinary type-IV collagen, lipocalin-type prostaglandin D synthase (L-PGDS), urinary neutrophil gelatinase-associated lipocalin (uNGAL),Annexin Al, Rab23, Shh, Ihh, Dhh, PTCH1, PTCH2, SMO, Gli1,Gli2, Gli3, TLR4, cystatin C, AQPI, AQP2, AQP3, NKCC2, NaPill,DAHKSEVAHRFKD [RNA:] SLC12A1, UMOD, vWF, MMPI, MMP3, SLC22A6, SLC22A8, SLC22A 12, podocin, cubulin, LRP2, AQP9, and albumin,carcinoembryonic antigen (CEA), mucin, alpha-fetoprotein,tyrosinase, melanoma associated antigen, mutated tumor protein 53,p21, PUMA, prostate-specific antigen (PSA) or thyroglobulin, vonVVillebrand factor (VWF), thrombin, factor VIII, plasmin, fibrin,osteopontin (SPP1), Rab23, Shh, Ihh, Dhh, PTCH1, PTCH2, SMO,Gli1, Gli2, Gli3 Liver miscellaneousCarnitine; Cholic Acid; Chenodeoxycholic, Deoxycholic, Lithocholic,failure/Glycocholic; Prostaglandin E₂; 13,14-dihydro-15-keto Prostaglandindisease A2; Prostaglandin B2; Prostaglandin F2a; 15-keto-ProstaglandinF2α; 6-keto-Prostaglandin Fla; Thromboxane B2; 11-dehydro-Thromboxane B2; Prostaglandin D2; Prostaglandin J2;15-deoxy-Al 2,14-Prostaglandin J2; 11β-Prostaglandin F2α; 5(S)-Hydroxyeicosatetraenoic acid; 5(S)-Hydroxyeicosapentaenoic acid;Leukotriene B4; Leukotriene B5; Leukotriene 04; Leukotriene D4;Leukotriene E4; Leukotriene F4; 12(S)-Hydroxyeicosatetraenoicacid; 12(S)-Hydroxyeicosapentaenoic acid; 15(S)-Hydroxyeicosatetraenoic acid; 15(S)-Hydroxyeicosapentaenoic acid;Lipoxin A4; 8(S)-Hydroxyeicosatetraenoic acid; 9-Hydroxyeicosatetraenoic acid; 11-Hydroxyeicosatetraenoic acid; 8-iso-Prostaglandin F2a; 9-Hydroxyoctadecadienoic acid; 13-Hydroxyoctadecadienoic acid; 20(S)-Hydroxyeicosatetraenoic acid;9,10-Epoxyoctadecenoic acid; 12,13-Epoxyoctadecenoic acid;12,13-Dihydroxyoctadecenoic acid; 5,6-Epoxyeicosatrienoic acid;11,12-Epoxyeicosatrienoic acid; 14,15-Epoxyeicosatrienoic acid;5,6-Dihydroxyeicosatrienoic acid; 8,9-Dihydroxyeicosatrienoic acid;11,12-Dihydroxyeicosatrienoic acid; 14,15-Dihydroxyeicosatrienoicacid; 14,15-Epoxyeicosatetraenoic acid; 17,18-Epoxyeicosatetraenoic acid; 14,15-Dihydroxyeicosatetraenoic acid;17,18-Dihydroxyeicosatetraenoic acid; 19,20-Dihydroxydocosapentaenoic acid; diacetylspermine, hemopexin, TLR4 Heartmiscellaneous SFRP-3, NT-proBNP, troponin T, SKITHRIHWESASLL (SEQ ID NO:failure 6), AHKSEVAHRFK (SEQ ID NO: 7), uroguanylin, BNP CardiovascularmiscellaneousmiR-378, miR-497, miR-21, miR-15b, miR-99a, miR 29a, miR-24, healthmiR-30b, miR-29c, miR-331.3p, miR-19a, miR-22, miR-126, let-7b,miR-502.3, and miR-652IL-16, sFas, Fas ligand, MCP-3, HGF, CTACK, EOTAXIN,adiponectin, IL-18, TIMP.4, TIMP.1, CRP, VEGF, and EGF salivaC-reactive protein (CRP); myoglobin (MYO), creatinine kinasemyocardial band (CK-MB), cardiac troponins (cTn), andmyeloperoxidase; TNF-α, and MMP-9; CD40 High saliva lysozyme bloodpressure Tiredness/ urine endorepellin fatigue salivaPPGKPQGPPPQGGNQPQGPPPPPGKPQ (SEQ ID NO: 1);GNPQGPSPQGGNKPQGPPPPPGKPQ (SEQ ID NO: 2);SPPGKPQGPPQQEGNKPQGPPPPGKPQ (SEQ ID NO: 3) urinehuman herpesvirus 6, human herpesvirus 7, humancytomegalovirus, and Epstein-Barr virus (EBV) miscellaneousGGHPPPP (SEQ ID NO: 4), ESPSLIA (SEQ ID NO: 5); Malnutrition Saliva sIgADepressive miscellaneous Secretogranin, VGF disorder Alzheimer's CSF,β-amyloid(1-42), β-amyloid(1-40), tau, phosphor-tau-181 disease serum,saliva Stress salivaCortisol, dehydro-androsteronesulfate; 17-ketosteroidsulfate;dehydro-epiandrostronesulfate; corticosteroid, 17-hydroxycorticosteroid, chromogranin A, alpha-amylase, secretaryIgA, lysozyme, growth hormone, oxytocin miscellaneousaldose reductase, apoptosis signal-regulating kinase 1, aquaporin 5,beta-endorphin, betaine GABA transporter, caspase recruitmentdomain protein 9, caspase 8, cyclin D, cyclooxygenase 2,cytochrome P450, cytochrome c, c-fos, c-jun, epidermal growthfactor receptor, ferritin, glucocorticoid receptor, glucose regulatedprotein 58, glucose regulated protein 75, glutathione 5-transferase p,GroEL, heat shock protein 25/27, heat shock protein 40, heat shockprotein 60, heat shock protein 70, heat shock protein 90, heat shocktranscription factor-1, heme oxygenase-1, interleukin 113, interleukin6, interleukin 8, interleukin 10, interleukin 12, laminin, leptin receptor,matrix metalloproteinase 9, metallothionein, Mek-1, Mekk-1,inducible nitric oxide synthase, peripheral benzodiazepine receptor,p38 MAPK, salivary alpha amylase, SAPK, serotonin, serotoninreceptor, substance P, superoxide dismutase Mn, superoxidedismutase Cu/Zn, superoxide dismutase EC, transforming growthfactor β, tumor suppressor p53, and vasoactive intestinal peptideCircadian saliva melatonin rhythm Bone UrinePyridinoline, deoxypyridinoline, collagen type 1 corss-linked N-turnover/telopeptide (NTX), collagen type 1 corss-linked C-telopeptide (CTX),Osteoporosisbone sialoprotein (BSP), Tartrate-resistant acid phosphatase 5b salivadeoxypyridinium (D-PYR) and osteocalcin (OC), hepatocyte growthfactor and interleukin-1 beta Muscle Serum,Myoglobin, creatine kinase (CK), lactate dehydrogenase (LDH), damageurinealdolase, troponin, carbonic anhydrase type 3 and fatty acid-bindingprotein (FABP), transaminases Exercise/ sweat urea athletic serumMyostatin, follistatin-like related gene activity saliva testosteronePerformance miscellaneousinterleukin-6, interleukin-1 beta, G-CSF, interferon-gamma, enhancementinterleukin-8, interleukin-9, MCP-1, MIP-beta, and/or TNF alpha EnergySerum AMPK balance Urine, pre-albumin, retinol binding protein, urea(protein sweat, excretion)/ feces energy miscellaneouscholesterol, lipoproteins, insulin, insulin C peptide, IGF bindingstatus/ proteins, e.g. IGF-BPI, liver enzymes metabolic state GrowthSaliva IGF-1 Andropause salivatestosterone; testosterone precursors such as pregnenolone,progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone,dehydroepiandrosterone (DHEA) and delta-4-androstene-3,17-dione; testosterone and dihydrotestosterone metabolites such as the17-ketosteroids androsterone and etiocholanolone, polar metabolitesin the form of diols, triols, and conjugates, as well estradiol,estrogens, androsteindione, cortisol, DHEA, FSH (follicle stimulatinghormone), LH (luteinizing hormone), and GnRH (gonadotropin-releasing hormone) Menopause Saliva Follicle stimulating hormone (FSH)Estrogen and progesterone, testosterone, free testosterone, anddehydroepiandrosterone sulfate (DHEAS), cortisol and dehydro-epiandrosterone (DHEA) Pregnancy/ Saliva progesterone fetal urinehuman chorionic gonadotropin, Levonorgestrel, alpha-fetoproteindevelopment serum estradiol Breast urine47D10 antigen, PTCD2, 5L025A20, NFKB2, RASGRP2, PDE7A, cancerMLL, PRKCE, GPATC3, PRI0285 and GSTA4, MIPEP, PLCB2,SLC25A19, DEF6, ZNF236, C18orf22, COX7A2, DDX11, TOP3A,C9orf6, UFC1, PFDN2, KLRD1, LOC643641, HSP90AB1, CLCN7,TNFAIP2, PRKCE, MRPL40, FBF1, ANKRD44, CCT5, USP40,UBXD4, LRCH1, MRPL4, SCCPDH, STX6, LOC284184, F1123235,GPATC3, CPSF4, CREM, HIST1H1D, HPS4, FN3KRP, ANKRD16,08 orf16, ATF71P2, PRI0285 Prostate Serum/Prostate specific antigen (PSA) cancer saliva UrinePCA3, GOLPH2, SPINK1, TMPRSS2:ERG Infections See Table B2 Dental Salivaaspartate aminotransferase (AST) and alkaline phosphatase (ALP), caries/uric acid and albumin; 12-HETE; MMP-8, TIMP-1, and ICTP periodontaldisease Heavy saliva lead, cadmium metal poisoning Drugs/ salivamarijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, drugamphetamine, heroin, methyltestosterone, mesterolone, morphine,metabolitescyclophosphamide metabolites, Haloperidol, barbiturates; antipyrine,caffeine, cisplatin, cyclosporine, diazepam, digoxin, methadone,phenytoin, theophylline, tolbutamide. Nicotine/cotinine, cannabis urinetrichloroethanol glucuronide, Anabolic steroids, Androstenedione,Benzodiazepines, Chlordiazepoxide, Lorazepam, Zidovudine Allergiessaliva Allergen-specific IgAs (see Tables B7 and 9)

In some instances, the biomarker that can be detected by the presentmethod is an antibody in a sample, e.g., a diagnostic sample, that isprobative for diagnosing a disease or health condition of the subjectfrom which the sample is derived.

Tables B4 provides a list of autoantibody targets, which can be used, inwhole or as an epitope fragment, as a capture agent in the presentmethod to measure the amount of the epitope-binding antibody analyte ina sample and thereby diagnose the associated disease or healthcondition, e.g., an autoimmune disease. In some cases, the disease orhealth condition is related to an immune response to an allergen. TableB5 provides a list of allergens, which can be used, in whole or as anepitope fragment, as a capture agent in the present method to measurethe amount of the epitope-binding antibody analyte in a sample andthereby diagnose the associated disease or health condition, e.g., anallergy. In certain instances, the disease or health condition isrelated to an infectious disease, where the infectious agent may bediagnosed based on information including the measured amount ofantibodies against one or more epitopes derived from the infectiousagent (e.g., lipopolysaccharides, toxins, proteins, etc.). Tables B6provides a list of infectious-agent derived epitopes which can be used,in whole or as an epitope fragment, as a capture agent in the presentmethod to measure the amount of the epitope-binding antibody analyte ina sample and thereby diagnose the associated disease or healthcondition, e.g., an infection. Other epitopes or antigens that may besuitable for use in the present diagnostic method are described in,e.g., PCT App. Pub. No. WO 2013164476, which is incorporated herein byreference.

TABLE B4 Diagnostic Autoantibody Epitopes Disease/condition AutoantibodyTargets Cancer ACAA2; ANXA13; AQP2; ASPA; BCL2; BCL2L1; BIK; CD160;CD37; CDK4; CDK6; CHEK2; CITED2; CNN2; CTSC; CTSZ; CycE2; ELK1; FGF10;FN1; GATA3; GJA1; GNRH1; GRB2, HBB; HBE1; HIST2H2AA; HPRT1; ID2; IER2;IFI27; IFITM1; IFITM2; IL15; IL18; IL8; IL9; KRT16; LALBA; LDHA; LDHB;LECT1; MAFK; Mage3; MAGEA3; MMP2; NPPB; OAS1, p21; p53; PCNA; PENK;PEX3; PHB; PHYH; PI3; PKBα; PLN; S100A7; SCAMP1; SCGB1A1; SLC38A5;SNRP2; SNX9; SST; SSTR2; TACSTD1; TNNC2; TOB1; TSG101; VDRIP; WNT2, p62and Koc; ZFP161, Ubiquilin-1, HOX- B6, YB-1, Osteonectin, ILF3 Squamouscell protein kinase C and p53-binding protein (TP53 BP), lymphoid blastcrisis lung carcinoma oncogene (LBC), Small cell lung SOX families B1and B2, MUC-1, cancer Lung cancer MUC-1, p53, surviving, LAMR1, annexinI, 14-3-3-theta; AKR1B10; GOT2; HNRPR; PDIA3; NME2; RTN4; HI1FX; G3BP;HSPCA; ACTN4; PGP9. 5; Colorectal cancer MUC-1, surviving, p-53;translationally controlled tumor protein; HSPC218; Ribosomal proteinS18; v-Fte-1; v-Fos transformation effector protein; MAGEA3, SSX2,NY-ESO-1, HDAC5, MBD2, TRIP4, NY-CO-45, KNSL6, HIP1R, Seb4D, KIAA1416,and LMNA; UCHL3 Hepatocellular fibrillarin and p330d/CENP-F,insulin-like growth factor II mRNA-binding carcinoma proteins (IMP) 1,IMP3 and p53, NOR-90, nucleophosmin/protein B23, cyclin B1, DNAtopoisomerase II (topo II), p62, HCC1, SG2NA, MAGE-C2, AF146731;AF219119; AF146019; Ligatin; AF220416; AF218421; AF257175; AF244135;AF243495; AF287265; AF258340; AF270491; AF286340; small nuclearRNA-associated sm-like protein; Dna J protein; CENP-F; translationallycontrolled tumor protein; LDH-A; Albumin; Hsp89αΔN; SEC63; AF100141; 14,5 kDa protein; GCF2; Metallopanstimulin 1; SMP-30 D31815; Cg1 protein,;C3VS protein; F1-ATPase, β subunit; Human ribosomal protein L10;Pre-apolipoprotein CIII; Galactose-1- phosphate-uridyl-transferase(GALT); DNA polymerase Δ, small subunit; Mitochondrial DNA Renal cancerAF257175; small nuclear RNA-associated sm-like protein; Dna J protein;smooth muscle protein 22-alpha (SM22-alpha); carbonic anhydrase I (CAI)Acute leukemia Rho GDP dissociation inhibitor 2, γ-actin, F-actincapping protein (CAPZA1), heterogeneous nuclear ribonucleoprotein L(hnRNP L), tubulin-α 6, PCNA Chronic KIAA1641; PIPMT; FosB; ZNF268;SEBD4; Ikaros; p75/LDEGF; CHIP; lymphocytic PYGB; ZNF148; KIAA0336;RPL11; FMNL; HGRG8 leukemia non-Hodgkin's CENP-F, lymphoma Multiplemyeloma NY-ESO-1 melanoma NY-ESO-1, MAGE-1, BAGE, GAGE, MART-1/melan A,gp100, and tyrosinase Pancreatic Calreticulin, DEAD-box protein 48(DDX48) cancer Ovarian cancer ACSBG1, AFP, CSNK1A1 L, DHFR, MBNL1, TP53,PRL, PSMC1, PTGFR, PTPRA, RAB7L1, and SCYL3, her2/neu, MUC1, c-myc,ECPKA, and NY-ESO-1, p53, UBQLN1, HOXB6, TOP2A, putative helicase-RUVBL(RUVBL), HMBA-inducible (HEXIM1), DDX5 and HDCMA Prostate cancer Bcl2,NY-ESO-1, survival protein lens epithelium-derived growth factor p75(LEDGF/p75), PRDX6/AOP2, clusterin, DJ-1, superoxide dismutase, alcoholdehydrogenase, HSP70, HSP27/HSPB1, lactoylglutathione lyase, glucose-regulated protein-78 kDa (GRP78), p62, Koc, and IMP1, α-Methylacyl-coenzyme A racemase and 5-α-reductase, AKRIA1; Brd2; C17 orf 25; CAPZA1;c-MYC; Cyclin A; Cyclin B1; Cyclin D1; Drebrin; eIF4G1; HIP1; HSPA8;Lactoylglutathione lyase; MAD-CT-1; MAD-CT-2; No55; P53; P62; P90; PP4R;PIP; PSA; RPL13a; RPL22; Survivin; Syntenin 1; TDP-43; VCP; vWF; Lage-1,and Xage-1; bromo domain-containing protein 2 (BRD2), ribosomal proteinsL22 and L13a, XP_373908 Breast cancer p53, c-myc, NY-ESO-1, BRCA1,BRCA2, HER2, MUC1, IGFBP-2, TOPO2α, ribosomal protein S6, eukaryoticelongation factor 2, eukaryotic elongation factor 2 kinase, and heatshock protein 90 (HSP90), Ku protein, topoisomerase I, and the 32-kDasubunit of replication protein A; CENP-F; AF146731; int-2, pentraxin I,integrin beta5, cathepsin L2 and S3 ribosomal protein; RNA-bindingprotein regulatory subunit (RS), DJ-1 oncogene, glucose-6-phosphatedehydrogenase, heat shock 70-kDa protein 1 (HS71), and dihydrolipoamidedehydrogenase Nasopharyngeal MAGE, HSP70, Fibronectin, CD44, EBVantigens carcinoma Oral cancer Cyclin B1, p53 Oral squamous p53 cellcarcinoma Head and neck CASP-8, SART-1, TREX1, 3′ repair exonuclease;BRAP (BRCA1 squamous cell associated): Nuclear localization protein;Trim 26 zinc finger domains; carcinoma GTF21 transcription factor.Murine homolog TF11-1; NSEP1 (YB-1) transcription factor; MAZtranscription factor associated with c-myc; SON (DBP-5; KIAA1019; NREBPDNA binding protein); NACA nascent polypeptide-associated complex; NUBP2nucleotide binding protein; EEF2 Translation elongation factor 2; GU2Putative RNA helicase; RPLI3A ribosomal protein; SFRS21P (CASP11; SIP1;SRRP1290 splicing factor); RPS12 ribosomal protein; MGC2835 RNAhelicase; TMF1, TATA modulatory factor; PRC1 regulator of cytokinesis;KRT14 keratin 14; Viniculin; H2AFY histone family member; SLK(KIAA02304) Ste related kinase; NOL3 (ARC) nuclear protein 3, apoptosisrepressor; DNAJA2 member of Hsp40 family; DNAJA1 member of HSP40 family;LINE-1 retrotransposon; MOG (HSPC 165) Homolog of yeast protein; LIMS1(PINCH): LIM and senescent antigen-like domain; COPB2 coatomer proteincomplex subunit protein; FLJ22548 hypothetical protein; C21orf97;FLJ21324; MGC15873; SSNA1 Sjogrens syndrome nuclear autoantigen 1;KIAA0530, zinc finger domain; rat stannin; hypothetical proteinDKFZp4340032; human FLJ23089; PC326 Esophageal NY-ESO-1; SURF1, HOOK2,CENP-F, ZIC2, hCLA-iso, Ki-1/57, enigma, cancer HCA25a, SPK, LOC146223and AGENCOURT_7565913 Metabolic GFAP syndrome/ prediabetes Diabetes Zntransporter 8, glutamic acid decarboxylase (GAD), CD38, gad65, IA2,insulin, MRPS31, ICA1, L-type voltage gated calcium channel; SNRPB2;DDX42; C11orf63; TCOF1; TSSK2; KDM4B; PDGFB; LTK; RPL14; VIM; GTF2I;BCL2L13; LARP6; DKFZP434K028; USP39; SERBP1; CCL19; GAD2; MCM10; ZNF688;PTEN; RP6-166C19.11; GIPC1; TIGD1; CCDC131; HTF9C; SOX5; MCF2L;TRAF3IP1; 6CKINE; ACY3; AMMECR1L; ARHGAP9; ASNS; BATF2; BMX; C9ORF25;CDC2; CHGB; CXORF38; CXORF56; DMD; ECHDC1; EIF3F; EPHA2; ERMN; FAM136A;(includes; EG: 84908); FILIP1; FLT1; GART; GIMAP6; GNG7; GTF2F1; HGS;IFI6; KDM4B; LACE1; LGALS1; LGALS7; LIMS2; LTK; LUC7L; NCAPG; (includes;EG: 64151); NME6; NUPL1; PAK4; PDE4DIP; PSIP1; RAB20; RNGTT; RPS3;SPG20; TALDO1; TBRG1; THAP1; TRAF3IP2; UBL4A; ZC3HC1; ZNF131; RAD51AP1;HADH; (HADH); C11orf16; (C11orf16); TAC3; ABR; ECE1; PPP1R2; GRINL1A;ABR; C19orf44; MUSTN1; ETHE1; BMI1; BAZ2B; ; TBC1D22A; CAMK2N2; ASS1;CCNY; MARK2; RAD51AP1; RAB38; RIOK1; HSP90AA1; C11orf74; ARID3A; LMOD1;CAPRIN1; ITGB3BP; MND1; SGK; NADK; MED9; LDHA; ARHGAP26; ANKRA2; CRY2;IL23A; DUSP14; ZBTB44; SIRT1; SLC2A3; GPR172B; CCDC89; BATF; HMOX1;ARRDC1; USF2; GBGT1; EDC3; SGIP1; GCGR; ZRANB2; NLGN4Y; GJB6; CDK10;PSG1; CCDC74A; DENND1C; MAP2K6 Autoimmune cardiac troponin I (cTnl)heart disease Immunoglobulin PRKD1, MATN2, DDX17, UBE2W, CDKN1 B, SOD2,FLOT2, IQCK, A nephropathy BLZF1, BRD9, CDS2, EFNA3, EIF4A2, FLU,LIMCH1, MAGEA4, MEF2D, MLLT6, MRPL28, MUTED, NKAIN4, PCTK1, PLXNA1,PODN, POLH, PRKD2, RNF1 1 3A, SEPT5, TNS1, TOM1, TRPV4, USP12, ZMYM3,CIAPIN1, GDI2, HSPA8, SERPINA5 and TGM1 End stage renal IGLC1; IGHG1;EDC3; IGHG1; APEX2; CD3D; TRIM21; IGKV1-5; IGHG3; disease CTLA-FC; CD7;CLIP4; MAPRE1; SNRPB2; IGHG1; ZBTB44; CD3D; IGHG1; TRAM1; ERR beta-;LBD; CNBP; OLFM1; IGHM; SIRT5; CEP290; PHLDA1 Glomerular nephritisAddison's 21-hydroxylase, P450-17α-hydroxylase (17OH) and P450-sidechain disease cleavage (SCC) Primary ovarian Jo-1, proteinase 3 (PR3)insufficiency Sjögren's IgA, IgG, IgM autoantibodies; IgA, lactoferrinand beta2-microglobulin; syndrome lysozyme C, and cystatin C, amylaseand carbonic anhydrase SSA/Ro; LA/SS-B Systemic lupus CDC25B, APOBEC3G,ARAF, BCL2A1, CLK1, CREB1, CSNK1G1, erythematosus CSNK2A1, CWC27, DLX4,DPPA2, EFHD2, EGR2, ERCC2, EWSR1, (SLE) EZH2, FES, FOS, FTHL17, GEM,GNA15, GNG4, HMGB2, HNRNPUL1, HOXB6, ID2, IFI35, IGF2BP3, IGHG1, JUNB,KLF6, LGALS7, LIN28A, MLLT3, NFIL3, NRBF2, PABPC1, PATZ1, PCGF2, PPP2CB,PPP3CC, PRM1, PTK2, PTPN4, PYGB, RET, RPL18A, RPS7, RRAS, SCEL, SH2B1,SMAD2, STAM, TAF9, TIE1, UBA3, VAV1, WT1, ZAP70, orZNRDI KIT, C6orf93,RPL34, DOM3Z, COPG2, DNCL12, RRP41; FBXO9; RALBP1, PIAS2; EEF1D; CONI;KATNB1; POLR2E; CCT3; KIAA0643; RPL37A, GTF2H2; MAP2K5; CDK3; RPS6KA1;MARK4, MTO1; MGC42105; NFE2L2; WDR45L, STK4, PFKFB3; NTRK3; MLF1;TRIM37, ACTL7B, RPL18A, CKS1B; TUBA1, NME6, SUCLA2, IGHG1, PRKCBP1;BAG3; TCEB3; RPL15, SSX4; MAP2K7; EEF1G; RNF38, PHLDA2, KCMF1; NUBP2,VPS45A SSA/Ro; dsDNA; Smith; histones; thrombin; v-Fos transformationeffector protein, tryptase, Sm antigen, beta 2; cardiolipin;glycoprotein I β2; Endothelial PC/activated PC receptor; human gammaenolase CREST centromere syndrome Systemic Type I topoisomerasesclerosis Primary biliary nucleoporin 62, Sp100 nuclear antigen,nucleoporin 210 kDa, mitochondria, cirrhosis mitochondrial pyruvatedehydrogenase (PDH) or E3 binding protein Dermatitis eTG herpetiformisMiller-Fisher ganglioside GQ1B Syndrome Wegener's c-ANCA granulomatosisNeuropathies ganglioside GD3, ganglioside GM1, GA1, GM2, MAG microscopicp-ANCA polyangiitis Polymyositis Signal recognition particlesscleromyositis exosome complex Signal recognition particles myasthenianicotinic acetylcholine receptor Signal recognition particles,muscle-specific gravis kinase (MUSK) Signal recognition particlesLambert-Eaton voltage-gated calcium channel (P/Q-type) myasthenicsyndrome Hashimoto's thyroid peroxidase thyroiditis Graves' disease TSHreceptor paraneoplastic Hu, Yo (cerebellar Purkinje Cells), amphiphysincerebellar syndrome encephalitis voltage-gated potassium channel (VGKC),N-methyl-D-aspartate receptor (NMDA) Sydenham's basal ganglia neuronschorea antiphospholipid glycoprotein 1 (2GPI), Endothelial PC/activatedPC receptor syndrome Systemic proteinase 3 (PR3) and myeloperoxidase(MPO) vasculitis Neuromyelitis aquaporin-4 Allergies Allergen-specificIgAs Rheumatoid Rheumatoid factor, cyclic citrullinated protein; humancartilage gp39 arthritis peptides and type II collagen; citrullinatedfibrinogen, citrullinated vimentin, citrulline-substituted filaggrinpeptides, hnRNP-A2/B1, BiP, tryptase Asthma tryptase Multiple sclerosismyelin basic protein, spectrin, fodrin, myelin oligodentrocyteglycoprotein, proteolipid protein (PLP), 2′,3′-cyclicnucleotide-phosphodiesterase (CNP), Glc(α1,4)Glc(α) (GAGA4),Glc(α1,6)Glc(α) (GAGA6) amyotrophic HMGB1 lateral sclerosis (ALS)Idiopathic platelet glycoprotein (GP) IIb/IIIa, GPIb/IX, GPIa/IIathrombocytopenic purpura Thrombosis thrombomodulin CardiovascularEndothelial PC/activated PC receptor; IL-1 alpha, alpha-actinin-2(aActn2); disease alpha-Myosin Heavy Chain (alpha-MHC-S 1); SI fragmentof alpha-Myosin Heavy Chain 6 (alpha-MHC6-SI); alpha-Myosin Heavy Chain7 (MyHC7) post- ELAVL2, ELAVL3, ELAVL4, Nova-1, Nova-2, Cdr1, Cdr2; andCdr3 streptococcal disease such as PANDAS, post- GABHSglomerulonephritis, rheumatic fever, autism and Syndenham's choreaParkinson's alpha-synuclein; myelin basic protein (MBP), proteolipidprotein (PLP), Disease myelin oligodendrocyte glycoprotein (MOG), myelinassociated glycoprotein (MAG), oligodendrocytes specific protein (OSP)pernicious Vitamin B₁₂ anemia

TABLE B5 Allergen Epitopes Source Allergen mites Acas13, Blot1, Blot3,Blot4, Blot5, Blot6, Blot10, Blot11, Blot12, Blot13, Blot19; Americanhouse dust mite (Derf1, Derf2, Derf3, Derf7, Derf10, Derf11, Derf14,Derf15, Derf16, Derf17, Derf18w); house dust mite (Derm1); Europeanhouse dust mite (Derp1, Derp2, Derp3, Derp4, Derp5, Derp6, Derp7, Derp8,Derp9, Derp10, Derp11, Derp14, Derp20, Derp21); mite (Eurm2; Eurm14);storage mite (Glyd2, Lepd2, Lepd5, Lepd7, Lepd10, Lepd13, Tyrp2,Tyrp13); Dermatophagoides farinae (Derf1.0101, Derf1.0102, Derf1.0103,Derf1.0104, Derf1.0105, Derf2.0101, Derf2.0102, Derf2.0103, Derf2.0104,Derf2.0105, Derf2.0106, Derf2.0107, Derf2.0108, Derf2.0109, Derf2.0110,Derf2.0111, Derf2.0112, Derf2.0113, Derf2.0114, Derf2.0115, Derf2.0116,Derf2.0117); Dermatophagoides pteronyssinus (Derp1.0101, Derp1.0102,Derp1.0103, Derp1.0104, Derp1.0105, Derp1.0106, Derp1.0107, Derp1.0108,Derp1.0109, Derp1.0110, Derp1.0111, Derp1.0112, Derp1.0113, Derp1.0114,Derp1.0115, Derp1.0116, Derp1.0117, Derp1.0118, Derp1.0119, Derp1.0120,Derp1.0121, Derp1.0122, Derp1.0123, Derp2.0101, Derp2.0102, Derp2.0103,Derp2.0104, Derp2.0105, Derp2.0106, Derp2.0107, Derp2.0108, Derp2.0109,Derp2.0110, Derp2.0111, Derp2.0112, Derp2.0113); Euroglyphus maynei(Eurm2.0101, Eurm2.0102); Glycyphagus domesticus (Glyd2.0101,Glyd2.0201); and Lepidoglyphus destructor (Lepd2.0101, Lepd2.0101,Lepd2.0101, Lepd2.0102, Lepd2.0201, Lepd2.0202) Pollen Short Ragweed(Ambrosia artemisiifolia) allergen, Amb a 1, Amba2, Amba3, Amba5, Amba6,Amba7, Amba8, Amba9, Amba10; Betula verrucosa allergen, Bet v 1, Phleumpratense allergen, Phl p 5), giant ragweed (Ambt5); mugwort (Artv1,Artv2, Artv3, Artv4, Artv5, Artv6); sunflower (Hela1, Hela2, Hela3);Mercurialis annua (Mera1); lamb's-quarters, pigweed (Chea1); whitegoosefoot (Chea2, Chea3); Russian-thistle (Salk1); Rosy periwinkle(Catr1); English plantain (Plal1); Japanese hop (Humj1); Parietariajudaica (Parj1, Parj2, Parj3); Parietaria officinalis (Paro1); Ambrosiaartemisiifolia (Amba8.0101, Amba8.0102, Amba9.0101, Amba9.0102);Plantago lanceolata (Plal1.0101, Plal1.0102, Plal1.0103); and Parietariajudaica (Parj1.0101, Parj1.0102, Parj1.0201, Par2.0101, Parj2.0102,Parj3.0101, Parj3.0102), Bermuda grass (Cynd1, Cynd7, Cynd12, Cynd15,Cynd22w, Cynd23, Cynd24); orchard grass (Dacg1, Dacg2, Dacg3, Dacg5);meadow fescue (Fesp4w); velvet grass (Holl1); rye grass (Lolp1, Lolp2,Lolp3, Lolp5, Lolp11); canary grass (Phaa1); Timothy (Phlp1, Phlp2,Phlp4, Phlp5, Phlp6, Phlp11, Phlp12, Phlp13); Kentucky blue grass(Poap1, Poap5); Johnson grass (Sorh1); Cynodon dactylon (Cynd1.0101,Cynd1.0102, Cynd1.0103, Cynd1.0104, Cynd1.0105, Cynd1.0106, Cynd1.0107,Cynd1.0201, Cynd1.0202, Cynd1.0203, Cynd1.0204); Holcus lanatus(Holl1.0101, Holl1.0102); Lolium perenne (Lolp1.0101, Lolp1.0102,Lolp1.0103, Lolp5.0101, Lolp5.0102); Phleum pretense (Phlp1.0101,Phlp1.0102, Phlp4.0101, Phlp4.0201, Phlp5.0101, Phlp5.0102, Phlp5.0103,Phlp5.0104, Phlp5.0105, Phlp5.0106, Phlp5.0107, Phlp5.0108, Phlp5.0201,Phlp5.0202); and Secale cereale (Secc20.0101, Secc20.0201), Alder(Alng1); Birch (Betv1, Betv2, Betv3, Betv4, Betv6, Betv7); hornbeam(Carb1); chestnut (Cass1, Cass5, Cass8); hazel (Cora1, Cora2, Cora8,Cora9, Cora10, Cora11); White oak (Quea1); Ash (Frae1); privet (Ligv1);olive (Olee1, Olee2, Olee3, Olee4, Olee5, Olee6, Olee7, Olee8, Olee9,Olee10); Lilac (Syrv1); Sugi (Cryj1, Cryj2); cypress (Cupa1); commoncypress (Cups1, Cups3w); mountain cedar (Juna1, Juna2, Juna3); pricklyjuniper (Juno4); mountain cedar (Juns1); eastern red cedar (Junv1);London plane tree (Plaa1, Plaa2, Plaa3); date palm (Phod2); Betulaverrucosa (Betv1.0101, Betv1.0102, Betv1.0103, Betv1.0201, Betv1.0301,Betv1.0401, Betv1.0402, Betv1.0501, Betv1.0601, Betv1.0602, Betv1.0701,Betv1.0801, Betv1.0901, Betv1.1001, Betv1.1101, Betv1.1201, Betv1.1301,Betv1.1401, Betv1.1402, Betv1.1501, Betv1.1502, Betv1.1601, Betv1.1701,Betv1.1801, Betv1.1901, Betv1.2001, Betv1.2101, Betv1.2201, Betv1.2301,Betv1.2401, Betv1.2501, Betv1.2601, Betv1.2701, Betv1.2801, Betv1.2901,Betv1.3001, Betv1.3101, Betv6.0101, Betv6.0102); Carpinus betulus(Carb1.0101, Carb1.0102, Carb1.0103, Carb1.0104, Carb1.0105, Carb1.0106,Carb1.0106, Carb1.0106, Carb1.0106, Carb1.0107, Carb1.0107, Carb1.0108,Carb1.0201, Carb1.0301, Carb1.0302); Corylus avellana (Cora1.0101,Cora1.0102, Cora1.0103, Cora1.0104, Cora1.0201, Cora1.0301, Cora1.0401,Cora1.0402, Cora1.0403, Cora1.0404); Ligustrum vulgare (Ligv1.0101,Ligv1.01.02); Olea europea (Olee1.0101, Olee1.0102, Olee1.0103,Olee1.0104, Olee1.0105, Olee1.0106, Olee1.0107); Syringa vulgaris(Syrv1.0101, Syrv1.0102, Syrv1.0103); Cryptomeria japonica (Cryj2.0101,Cryj2.0102); and Cupressus sempervirens (Cups1.0101, Cups1.0102,Cups1.0103, Cups1.0104, Cups1.0105) mold Alternaria alternata allergen,Alt a 1, Alta3, Alta4, Alta5, Alta6, Alta7, Alta8, Alta10, Alta12,Alta13, Aspergillus fumigatus allergen, Asp f 1, Aspf2, Aspf3, Aspf4,Aspf5, Aspf6, Aspf7, Aspf8, Aspf9, Aspf10, Aspf11, Aspf12, Aspf13,Aspf15, Aspf16, Aspf17, Aspf18, Aspf22w, Aspf23, Aspf27, Aspf28,Aspf29); Aspergillus niger (Aspn14, Aspn18, Aspn25); Aspergillus oryzae(Aspo13, Aspo21); Penicillium brevicompactum (Penb13, Penb26);Penicillium chrysogenum (Pench13, Pench18, Pench20); Penicilliumcitrinum (Penc3, Penc13, Penc19, Penc22w, Penc24); Penicillium oxalicum(Peno18); Fusarium culmorum (Fuse1, Fusc2); Trichophyton rubrum (Trir2,Trir4); Trichophyton tonsurans (Trit1, Trit4); Candida albicans (Canda1,Canda3); Candida boidinii (Candb2); Psilocybe cubensis (Psic1, Psic2);shaggy cap (Copd, Copc2, Copc3, Copc5, Copc7); Rhodotorula mucilaginosa(Rhom1, Rhom2); Malassezia furfur (Malaf2, Malaf3, Malaf4); Malasseziasympodialis (Malas1, Malas5, Malas6, Malas7, Malas8, Malas9, Malas10,Malas11, Malas12, Malas13); Epicoccum purpurascens (Epip1); andAlternaria alternate (Alta1.0101, Alta1.0102), Aspergillus versicolorantigen, S. chartarum antigen), Cladosporium herbarum (Clah2, Clah5,Clah6, Clah7, Clah8, Clah9, Clah10, Clah12); Aspergillus flavus(Aspf113); mammals Bos domesticus dander allergen, Bos d 2, Bosd3,Bosd4, Bosd5, Bosd6, Bosd7, Bosd8, Bosd2.0101, Bosd2.0102, Bosd2.0103,Canis familiaris allergen, Can f 1, Canf2, Canf3, Canf4, Equus caballusallergen, Equc1, Equc2, Equc3, Equc4, Equc5, Felis domesticus allergen,Fel d 1, Feld2, Feld3, Feld4, Feld5w, Feld6w, Feld7w, guinea pig (Cavp1,Cavp2); Mouse Urinary Protein (MUP, Musm1) allergen, Mus m 1, RatUrinary Protein (RUP, Ratn1) allergen, Rat n 1., Equus caballus(Equc2.0101, Equc2.0102)) Insects Mosquito (Aeda1, Aeda2); honey bee(Apim1, Apim2, Apim4, Apim6, Apim7); bumble bee (Bomp1, Bomp4); Germancockroach (Blag1, Blag2, Blag4, Blag5, Blag6, Blag7, Blag8); Americancockroach (Pera1, Pera3, Pera6, Pera7); midge (Chit1-9, Chit1.01,Chit1.02, Chit2.0101, Chit2.0102, Chit3, Chit4, Chit5, Chit6.01,Chit6.02, Chit7, Chit8, Chit9); cat flea (Ctef1, Ctef2, Ctef3); pineprocessionary moth (Thap1); silverfish (Leps1); white face hornet(Dolm1, Dolm2, Dolm5); yellow hornet (Dola5); wasp (Pola1, Pola2, Pola5,Pole1, Pole5, Polf5, Polg5, Polm5, Vesvi5); Mediterranean paper wasp(Pold1, Pold4, Pold5); European hornet (Vespc1, Vespc5); giant asianhornet (Vespm1, Vespm5); yellowjacket (Vesf5, Vesg5, Vesm1, Vesm2,Vesm5, Vesp5, Vess5, Vesv1, Vesv2, Vesv5); Australian jumper ant (Myrp1,Myrp2); tropical fire ant (Solg2, Solg4); fire ant (Soli2, Soli3,Soli4); Brazilian fire ant (Sols2); California kissing bug (Triap1);Blattella germanica (Blag1.0101, Blag1.0102, Blag1.0103, Blag1.02,Blag6.0101, Blag6.0201, Blag6.0301); Periplaneta Americana (Pera1.0101,Pera1.0102, Pera1.0103, Pera1.0104, Pera1.02, Pera3.01, Pera3.0201,Pera3.0202, Pera3.0203, Pera7.0101, Pera7.0102); Vespa crabo(Vespc5.0101, Vespc5.0101); and Vespa mandarina (Vesp m 1.01, Vesp m1.02) Rubber rubber (latex)(Hevb1, Hevb2, Hevb3, Hevb4, Hevb5, Hevb6.01,Hevb6.02, Hevb6.03, Hevb7.01, Hevb7.02, Hevb8, Hevb9, Hevb10, Hevb11,Hevb12, Hevb13); Hevea brasiliensis (Hevb6.01, Hevb6.0201, Hevb6.0202,Hevb6.03, Hevb8.0101, Hevb8.0102, Hevb8.0201, Hevb8.0202, Hevb8.0203,Hevb8.0204, Hevb10.0101, Hevb10.0102, Hevb10.0103, Hevb11.0101,Hevb11.0102) Others Nematode (Anis1, Anis2, Anis3, Anis4); pigeon tick(Argr1); worm (Ascs1); papaya (Carp1); soft coral (Denn1); humanautoallergens (Homs1, Homs2, Homs3, Homs4, Homs5); obeche (Trips1)

TABLE B6 Infectious Agent-derived Epitopes Infectious Agent EpitopeMycobacterium tuberculosis isocitrate dehydrogenase (ICDs) Influenzavirus Hemagglutinin (H1), neuraminidase (N1) Dengue virus envelope (E)Toxoplasma gondii microneme proteins, SAG1, SAG2, GRA1, GRA2, GRA4,GRA6, GRA7, GRA3, ROP1, ROP2, p30, MIC3, MIC2, M2AP, p29, p35, p66Entamoeba histolytica M17, neutral thiol proteinase Streptococcuspneumonia Pneumolysin, pneumococcal histidine triad D (PhtD),pneumococcal choline-binding protein A (PcpA), pneumococcal histidinetriad E (PhtE), LytB Mycoplasma pneumonia exotoxin Epstein-Barr virusVCA Helicobacter pylori CagA, Vacuolating protein, ureB, hsp60, ureH,urea, ferritin like protein Campylobacter jejuni PEB1, PEB3 Bacillusanthracis SAP SARS virus RNA-dependent replicases Ia and Ib, spike (S)protein, small envelope (E) protein, membrane (M) protein, andnucleocapsid (N) protein Ebola virus Nucleoprotein N Schmallenberg virusN nucleoprotein enterovirus 71 VPI protein Japanese Encephalitis virussoluble E protein, envelope E protein Ross River virus soluble E2protein Mayaro virus soluble E2 protein Equine Encephalitis virusessoluble E2 protein Akabane virus N nucleoprotein human betacoronavirusNucleoprotein N, protein S Hepatitis C virus protein C, core antigenHepatitis E virus protein C Plasmodium falciparum MSP-1 + AMA-1 proteinLeptospira interrogans HbpA, LruA, LruB, or LipL32

In some instances, the biomarker to be detected using the present methodis a micro RNA (miRNA) biomarker that is associated with a disease or ahealth condition. The following Table B7 provides a list of miRNAbiomarker that can be detected using the present invention, and theirassociated diseases/health conditions.

TABLE B7 Diagnostic miRNA Markers Disease/Condition Marker* Breastcancer miR-10b, miR-21, miR-125b, miR-145, miR-155, miR-191, miR-382,MiR-1, miR-133a, miR-133b, miR-202, miR-1255a, miR-671-3p, miR- 1827,miR-222, miR-744, miR-4306, miR-151-3p, miR-130, miR-149, miR-652,miR-320d, miR-18a, miR-181a, miR-3136, miR-629, miR-195, miR-122,miR-375, miR-184, miR-1299, miR381, miR-1246, miR-410, miR-196a,miR-429, miR-141, miR-376a, miR-370, miR-200b, miR- 125a-5p, miR-205,miR-200a, miR-224, miR-494, miR-216a, miR-654- 5p, miR-217, miR-99b,miR-885-3p, miR-1228, miR-483-5p, miR-200c, miR-3065-5p, miR-203,miR-1308, let-7a, miR-17-92, miR-34a, miR- 223, miR-150, miR-15b,miR-199a-5p, miR-33a, miR-423-5p, miR-424, let-7d, miR-103, miR-23b,miR-30d, miR-425, miR-23a, miR-26a, miR- 339-3p, miR-127-3p, miR-148b,miR-376a, miR-376c, miR-409-3p, miR-652, miR-801 (miR-92a, miR-548d-5p,miR-760, miR-1234, miR-18b, miR-605, miR- 193b, miR-29) Leukemia miR-98,miR-155, miR-21, let-7, miR-126, miR-196b, miR-128, miR- 195, miR-29a,miR-222, miR-20a, miR-150, miR-451, miR-135a, miR- 486-5p, miR-92,miR-148a, miR-181a, miR-20a, miR-221, miR-625, miR-99b (miR-92a, miR-15,miR-16, miR-15a, miR-16-1, miR-29) Multiple myeloma miR-15a, miR-16,miR-193b-365, miR-720, miR-1308, miR-1246, miR- 1, miR-133a, miR-221,miR-99b, Let-7e, miR-125a-5p, miR-21, miR- 181a/b, miR-106b-25, miR-32,miR-19a/b, miR-17-92, miR-17, miR-20, miR-92, miR-20a, miR-148a,miR-153, miR-490, miR-455, miR-642, miR-500, miR-296, miR-548d, miR-373,miR-554, miR-888, miR-203, miR-342, miR-631, miR-200a, miR-34c, miR-361,miR-9*, miR-200b, miR-9, miR-151, miR-218, miR-28-3p, miR-200c, miR-378,miR-548d- 5p, miR-621, miR-140-5p, miR-634, miR-616, miR-130a, miR-593,miR- 708, miR-200a*, miR-340, miR-760, miR-188-5p, miR-760, miR-885-3p,miR-590-3p, miR-885-5p, miR-7, miR-338, miR-222, miR-99a, miR- 891a,miR-452, miR-98, miR-629, miR-515-3p, miR-192, miR-454, miR- 151-3p,miR-141, miR-128b, miR-1227, miR-128a, miR-205, miR-27b, miR-608,miR-432, miR-220, miR-135a, miR-34a, miR-28, miR-412, miR-877,miR-628-5p, miR-532-3p, miR-625, miR-34b, miR-31, miR- 106b, miR-146a,miR-210, miR-499-5p, miR-140, miR-188, miR-610, miR-27a, miR-142-5p,miR-603, miR-660, miR-649, miR-140-3p, miR- 300, miR-335, miR-206,miR-20b, miR-130b, miR-183, miR-652, miR- 133b, miR-191, miR-212,miR-194, miR-100m miR-1234m miR-182m miR-888, miR-30e-5p, miR-574,miR-135b, miR-125b, miR-502m miR- 320, miR548-421, miR-129-3p, miR-190b,miR-18a, miR-549, 338-5p, miR-756-3p, miR-133a, miR-521, miR-486-3p,miR-553, miR-452*, miR-628-3p, miR-620, miR-566, miR-892a,miR-miR-339-5p, miR-628, miR-520d-5p, miR-297, miR-213, miR-519e*,miR-422a, miR-198, miR- 122a, miR-1236, miR-548c-5p, miR-191*, miR-583,miR-376c, miR-34c- 3p, miR-453, miR-509, miR-124a, miR-505, miR-208,miR-659, miR- 146b, miR-518c, miR-665, miR-324-5p, miR-152, miR-548d,miR-455- 3p (miR-15a, miR-373*, miR-378*, miR-143, miR-337, miR-223,miR-369- 3p, miR-520g, miR-485-5p, miR-524, miR-520h, miR-516-3p, miR-519d, miR-371-3p, miR-455, miR-520b, miR-518d, miR-624, miR-296, miR-16)monoclonal miR-21, miR-210, miR-9*, miR-200b, miR-222, miR-376gammopathy of (miR-339, miR-328) undetermined significanceMyelodisplastic (Let-7a, miR-16) syndrome Lymphoma miR-155, miR-210,miR-21, miR-17-92, miR-18a, miR-181a, miR-222, miR-20a/b, miR-194,miR-29, miR-150, miR-155, miR-223, miR-221, let-7f, miR-146a, miR-15,miR-16-1, miR-34b/c, miR-17-5p (miR-20b, miR-184, miR-200a/b/c, miR-205,miR-34a, miR-29a, miR- 29b-1, miR-139, miR-345, miR-125a, miR-126,miR-26a/b, miR-92a, miR-20a, miR-16, miR-101, miR-29c miR-138, miR-181b)Lung cancer let-7c, miR-100, miR-10a, miR-10b, miR-122a, miR-125b,miR-129, miR-148a, miR-150, miR-17-5p, miR-183, miR-18a*, miR-18b,miR-190, miR-192, miR-193a, miR-196b, miR-197, miR-19a, miR-19b,miR-200c, miR-203, miR-206, miR-20b, miR-210, miR-214, miR-218, miR-296,miR-30a-3p, miR-31, miR-346, miR-34c, miR-375, miR-383, miR-422a,miR-429, miR-448, miR-449, miR-452, miR-483, miR-486, miR-489, miR-497,miR-500, miR-501, miR-507, miR-511, miR-514, miR-516-3p, miR-520d,miR-527, miR-7, miR-92, miR-93, miR-99a, miR-25, miR- 223, miR-21,miR-155, miR-556, miR-550, miR-939, miR-616*, miR- 146b-3p andmiR-30c-1*, miR-142-5p, miR-328, miR-127, miR-151, miR-451, miR-126,miR-425-5p, miR-222, miR-769-5p, miR-642, miR- 202, miR-34a (let-7a,let-7d, let-7e, let-7g, let-7i, miR-1, miR-103, miR-106a, miR- 125a,miR-130a, miR-130b, miR-133a, miR-145, miR-148b, miR-15a, miR-15b,miR-17-3p, miR-181d, miR-18a, miR-196a, miR-198, miR- 199a, miR-199a*,miR-212, miR-22, miR-221, miR-23a, miR-23b, miR- 26a, miR-27a, miR-27b,miR-29b, miR-30b, miR-30d, miR-30e-3p, miR- 320, miR-323, miR-326,miR-331, miR-335, miR-339, miR-374, miR- 377, miR-379, miR-410, miR-423,miR-433, miR-485-3p, miR-485-5p, miR-487b, miR-490, miR-491, miR-493,miR-493-3p, miR-494, miR- 496, miR-502, miR-505, miR-519d, miR-539,miR-542-3p, miR-98) Colorectal cancer miR-29a, miR-17-3p, miR-92,miR-21, miR-31, miR-155, miR-92a, miR- 141, mir-202, mir-497, mir-3065,mir-450a-2, mir-3154, mir-585, mir- 3175, mir-1224, mir-3117, mir-1286(miR-34) Prostate cancer miR-141, miR-375, miR-16, miR-92a, miR-103,miR-107, miR-197, miR- 485-3p, miR-486-5p, miR-26a, miR-92b, miR-574-3p,miR-636, miR- 640, miR-766, miR-885-5p, miR-141, miR-195, miR-375,miR-298, miR- 346, miR-1-1, miR-1181, miR-1291, miR-133a-1, miR-133b,miR-1469, miR-148*, miR-153, miR-182, miR-182*, miR-183, miR-183*,miR-185, miR-191, miR-192, miR-1973, miR-200b, miR-205, miR-210,miR-33b*, miR-3607-5p, miR-3621, miR-378a, miR-429, miR-494, miR-582,miR- 602, miR-665, miR-96, miR-99b*, miR-100, miR-125b, miR-143, miR-200a, miR-200c, miR-222, miR-296, and miR-425-5p Ovarian cancer miR-21,miR-92, miR-93, miR-126, miR-29a, miR-141, miR-200a/b/c, miR-203,miR-205, miR-214, miR-221, miR-222, miR-146a, miR-150, miR-193a-5p,miR-31, miR-370, let-7d, miR-508-5p, miR-152, miR- 509-3-5p, miR-508-3p,miR-708, miR-431, miR-185, miR-124, miR-886- 3p, hsa-miR-449,hsa-miR-135a, hsa-miR-429, miR-205, miR-20b, hsa- miR-142-5p, miR-29c,miR-182 (miR-155, miR-127, miR-99b) Cervical cancer miR-21, miR-9,miR-200a, miR-497 (miR-143, miR-203, miR-218) Esophageal miR-21,hsa-miR-200a, hsa-miR-345, hsa-miR-373*, hsa-miR-630, hsa- carcinomamiR-663, hsa-miR-765, hsa-miR-625, hsa-miR-93, hsa-miR-106b, hsa-miR-155, hsa-miR-130b, hsa-miR-30a, hsa-miR-301a, hsa-miR-15b (miR-375)Gastric cancer miR-17-5p, miR-21, miR-106a, miR-106b, miR-187,miR-371-5p, miR- 378 (let-7a, miR-31, miR-192, miR-215, miR-200/141)Pancreatic cancer, miR-210, miR-21, miR-155, miR-196a, miR-1290,miR-20a, miR-24, ductal miR-25, miR-99a, miR-185, miR-191, miR-18a,miR-642b-3p, miR-885- adenocarcinoma 5p, miR-22-3p, miR-675, miR-212,miR-148a*, miR-148, miR-187, let- 7g*, miR-205, miR-944, miR-431,miR-194*, miR-769-5p, miR-450b-5p, miR-222, miR-222*, miR-146, miR-23a*,miR-143*, miR-216a, miR- 891a, miR-409-5p, miR-449b, miR-330-5p,miR-29a*, miR-625 Hepatocellular miR-500, miR-15b, miR-21, miR-130b,miR-183, miR-122, miR-34a, carcinoma miR-16, miR-221, miR-222 MelanomamiR-150, miR-15b, miR-199a-5p, miR-33a, miR-423-5p, miR-424, miR-let-7d, miR-103, miR-23b, miR-30d, miR-425, miR-222, miR-23a, miR- 26a,miR-339-3p Squamous cell miR-184a carcinoma Bladder cancer miR-126,miR-182 (urine), miR-16, miR-320 (miR-143, miR-145, miR-200/141) Renalcancer miR-1233, miR-199b-5p, miR-130b (miR-10b, miR-139-5p) Oral cancermiR-31, miR-24, miR-184; miR-34c; miR-137; miR-372; miR-124a; miR- 21;miR-124b; miR-31; miR-128a; miR-34b; miR-154; miR-197; miR- 132;miR-147; miR-325; miR-181c; miR-198; miR-155; miR-30a-3p; miR-338;miR-17-5p; miR-104; miR-134; miR-213 (miR-200a, miR-125a, miR-133a;miR-99a; miR-194; miR-133; miR- 219; miR-100; miR-125; miR-26b; miR-138;miR-149; miR-195; miR- 107; and miR-139 (saliva)) Head and neckmiR-455-3p, miR-455-5p, miR-130b, miR-130b*, miR-801, miR-196a, cancermiR-21, miR-31 Endometrial cancer miR-503, miR-424, miR-29b, miR-146a,miR-31 Testicular cancer miR-372, miR-373 Glioblastoma miR-21, miR-221,miR-222 Thyroid cancer miR-187, miR-221, miR-222, miR-146b, miR-155,miR-224, miR-197, miR-192, miR-328, miR-346, miR-512-3D, miR-886-5p,miR-450a, miR- 301 b, miR-429, miR-542-3p, miR-130a, miR-146b-5p,miR-199a-5p, miR-193a-3p, miR-152, miR-199a-3p/miR-199b-3p, miR-424,miR-22, miR-146a, miR-339-3p, miR-365, let-7i*, miR-363*, miR-148a,miR-299- 3p, let-7a*, miR-200b, miR-200c, miR-375, miR-451, miR-144,let-7i, miR-1826, miR-1201, miR-140-5p, miR-126, miR-126*, let-7f-2*,miR- 148b, miR-21*, miR-342-3p, miR-27a, miR-145*, miR-513b, miR-101,miR-26a, miR-24, miR-30a*, miR-377, miR-518e7, miR-519a7, miR- 519b-5p,miR-519c-5p, miR-5227, miR-523*, miR-222*, miR-452, miR- 665, miR-584,miR-492, miR-744, miR-662, miR-219-2-3p, miR-631 and miR-637,miRPlus-E1078, miR-19a, miR-501-3p, miR-17, miR-335, miR-106b, miR-15a,miR-16, miR-374a, miR-542-5p, miR-503, miR- 320a, miR-326, miR-330-3p,miR-1, miR-7b, miR-26b, miR-106a, miR-139, miR-141, miR-143, miR- 149,miR-182, miR-190b, miR-193a, miR-193b, miR-211, miR-214, miR-218,miR-302c*, miR-320, miR-324, miR-338, miR-342, miR-367, miR-378,miR-409, miR-432, miR-483, miR-486, miR-497, miR-518f, miR-574, miR-616,miR-628, miR-663b, miR-888, miR-1247, miR-1248, miR-1262, and miR-1305miR-21, miR-25, miR-32, miR-99b*, miR-125a, miR-125b, miR-138, miR-140,miR-181a, miR-213, miR-221, miR-222, and miR-345 Ischemic heart miR-1,miR-30c, miR-133, miR-145, miR-208a/b, miR-499, miR-663b,disease/Myocardial miR-1291 infarction (miR-126, miR-197, miR-223) Heartfailure miR-29b, miR-122, miR-142-3p, miR-423-5p, miR-152, miR-155, miR-497 (miR-107, miR-125b, miR-126, miR-139, miR-142-5p, miR-497) StrokemiR-124, miR-145 (miR-210) Coronary artery miR-21, miR-27b, miR-130a,miR-134, miR-135a, miR-198, miR-210, disease miR-370 (miR-17, miR-92a,miR-126, miR-145m miR-155m miR-181a, miR-221, miR-222) Diabetes miR-9,miR-28-3p, miR-29a, miR-30d, miR-34a, miR-124a, miR-146a, miR-375,miR-503, 144 (miR-15a, miR-20b, miR-21, miR-24, miR-126, miR-191,miR-197, 223, miR-320, miR-486) Hypertension Hcmv-miR-UL112, Let-7e(miR-296-5p) Chronic HCV miR-155, miR-122, miR-125b, miR-146a, miR-21infection Liver injury miR-122, miR-192 Sepsis miR-146a, miR223Arthritis miR-125a-5p, miR-24, miR-26a, miR-9, miR-25, miR-98, miR-146a,miR-124a, miR-346, miR-223, miR-155 (miR-132, miR-146) Systemic lupus(miR-200a/b/c, miR-205, miR-429, miR-192, miR-141, miR-429, miR-erythematosus 192 (urine or serum)) Chron disease miR-199a-5p,miR-362-3p, miR-532-3p, miR-plus-E1271, miR-340* (miR-149*,miR-plus-F1065) Ulcerative colitis miR-28-5p, miR-151-5p, miR-199-5p,miR-340*, miR-plus-E1271, miR- 103-2*, miR-362-3p, miR-532-3p (miR-505)Asthma miR-705, miR-575, let-7d, miR-173p, miR-423-5p, miR-611, miR-674,let-7f-1, miR-23b, miR-223, miR-142-3p, let-7c, miR-25, miR-15b, let-7g, and miR-542-5p, miR-370 (miR-325, miR-134, miR-198, miR-721,miR-515-3p, miR-680, miR-601, miR-206, miR-202, miR-671, miR-381,miR-630, miR-759, miR-564, miR-709, miR-513, miR-298) Chronic pulmonarymiR-148a, miR-148b, miR-152 disease Idiopathic miR-199a-5p pulmonaryfibrosis Alzheimer's disease (miR-137, miR-181c, miR-9, miR-29a/b)Duchenne muscular miR-1, miR-133a, miR-206 dystrophy Multiple sclerosismiR-633, miR-181c-5p (CSF), miR-17-5p, miR-193a, miR-326, miR- 650,miR-155, miR-142-3p, miR-146a, miR-146b, miR-34a, miR-21, miR-23a,miR-199a, miR-27a, miR-142-5p, miR-193a, miR-15a, miR- 200c, miR-130a,miR-223, miR-22, miR-320, miR-214, miR-629, miR- 148a, miR-28, miR-195,miR-135a, miR-204, miR-660, miR-152, miR- 30a-5p, miR-30a-3p, miR-365,miR-532, let-7c, miR-20b, miR-30d, miR- 9, hsa-mir-18b, hsa-mir-493,hsa-mir-599, hsa-mir-96, hsa-mir-193, hsa-mir-328, hsa-mir-409-5p,hsa-mir-449b, hsa-mir-485-3p, hsa-mir- 554 (miR-922 (CSF), miR-497,miR-1 and miR-126, miR-656, miR-184, miR-139, miR-23b, miR-487b,miR-181c, miR-340, miR-219, miR-338, miR-642, miR-181b, miR-18a,miR-190, miR-213, miR-330, miR-181d, miR-151, miR-140) PreeclampsiamiR-210 (miR-152) Gestational diabetes (miR-29a, miR-132) Plateletactivity miR-126, miR-197, miR-223, miR-24, miR-21 Pregnancy/placenta-miR-526a, miR-527, miR-520d-5p, miR-141, miR-149, miR-299-5p, derivedmiR-517a Drug treatment for miR-130a, miR-146b, miR-143, miR-145,miR-99b, miR-125a, miR-204, immunomodulation miR-424, miR-503 Aging(miR-151a-3p, miR-181a-5p, miR-1248) *miRNA markers in parentheses aredownregulated

Environmental Testing.

As summarized above, the devices, systems and methods in the presentinvention can find use in analyzing an environmental sample, e.g., asample from water, soil, industrial waste, etc., for the presence ofenvironmental markers. An environmental marker can be any suitablemarker, that can be captured by a capturing agent that specificallybinds the environmental marker in a CROF device configured with thecapturing agent. The environmental sample can be obtained from anysuitable source, such as a river, ocean, lake, rain, snow, sewage,sewage processing runoff, agricultural runoff, industrial runoff, tapwater or drinking water, etc. In some embodiments, the devices andsystems in the present invention detect the concentration of lead ortoxins in water. In some embodiments, the presence or absence, or thequantitative level of the environmental marker in the sample can beindicative of the state of the environment from which the sample wasobtained. In some cases, the environmental marker can be a substancethat is toxic or harmful to an organism, e.g., human, companion animal,plant, etc., that is exposed to the environment. In some cases, theenvironmental marker can be an allergen that can cause allergicreactions in some individuals who are exposed to the environment. Insome instances, the presence or absence, or the quantitative level ofthe environmental marker in the sample can be correlated with a generalhealth of the environment. In such cases, the general health of theenvironment can be measured over a period of time, such as week, months,years, or decades.

In some embodiments, the devices, systems and methods in the presentinvention further includes receiving or providing a report thatindicates the safety or harmfulness for a subject to be exposed to theenvironment from which the sample was obtained based on informationincluding the measured amount of the environmental marker. Theinformation used to assess the safety risk or health of the environmentcan include data other than the type and measured amount of theenvironmental marker. These other data can include the location,altitude, temperature, time of day/month/year, pressure, humidity, winddirection and speed, weather, etc. The data can represent an averagevalue or trend over a certain period (minutes, hours, days, weeks,months, years, etc.), or an instantaneous value over a shorter period(milliseconds, seconds, minutes, etc.).

The report can be generated by the device configured to read the CROFdevice, or can be generated at a remote location upon sending the dataincluding the measured amount of the environmental marker. In somecases, an expert can be at the remote location or have access to thedata sent to the remote location, and can analyze or review the data togenerate the report. The expert can be a scientist or administrator at agovernmental agency, such as the US Centers for Disease Control (CDC) orthe US Environmental Protection Agency (EPA), a research institution,such as a university, or a private company. In certain embodiments, theexpert can send to the user instructions or recommendations based on thedata transmitted by the device and/or analyzed at the remote location.

A list of exemplary environmental markers is set forth in Table 8 ofU.S. provisional application Ser. No. 62/234,538, filed on Sep. 29,2015, which application is incorporated by reference herein.

TABLE B8 Environmental Markers Class/Source Marker Synthetic17beta-estradiol (E2), estrone (EI), estrogen (ES: EI + E2 + estriol(E3)), 1 hormone 7alfa-ethynylestradiol (EE2), 4-nonylphenpol,testosterone analogues Halogenated p,p′-DDE, p,p′-DDD, p,p′-DDT,o,p′-DDE, o,p′-DDE, o,p′-DDT, o,p′-DDD, hydrocarbons chlordane,nonachlor, oxychlordane, heptachlor, heptachlor epoxide,pentachloroanisole, hexachlorobenzene, heptachlorbenzene, o,p′-methoxychlor, p,p′-methoxychlor, Hexachlorocyclopentadiene Pesticidesmanganese ethylene-bis-dithiocarbamate, diazinon, chlorphyrifos,carbofuran, carbaryl, malathion, dieldrin, fipronil, desulfinylfipronil,fipronil sulfide, fipronil sulfone, aldicarb, aldicarb sulfone, aldicarbsulfoxide, carbaryl, 3- hydroxycarbofuran, methiocarb, methomyl, ,oxamyl, propoxur, alpha-HCH, gamma-HCH, beta-HCH, delta-HCH,azinphos-methyl, chlorpyrifos, disulfoton, parathion, fonofos, ethoprop,parathion-methyl, phorate, terbufos, cis- permethrin, trans-permethrin,propargite, aldrin, chloroneb, endosulfan I, endrin, isodrin, mirex,toxaphene, lindane, O-ethyl O-4-nitrophenyl phenylphosphono-thioate(EPN), fenitrothion, pirimiphos-methyl, deltamethrin Herbicideacetochlor, alachlor, metolachlor, atrazine, deethylatrazine, cyanazine,terbuthylazine, terbutryn, metribuzin, bentazon, EPTC, triflualin,molinate norflurazon, simazine, prometon, promteryn, tebuthiuron, 2,4-D,diuron, dacthal, bromacil, deisopropyl atrazine, hydroxyatrazine,deethylhydroxyatrazine, deisopropylhydroxyatrazine, acetochlor ESA,acetochlor OA, alachlor ESA, alachlor OA, metolachlor ESA, metolachlorOA, 2,6-diethylaniline, napropamide, pronamide, propachlor, propanilmbutylate, pebulate, propham, thiobencarb, triallate, dacthal, dacthalmonoacid, 2,4-DB, dischlorprop, MCPA, MCPB, 2,4,5-T, 2,4,5-TP,benfluralin, ethalfluralin, oryzalin, pendimethalin, trifluralin,bentazon, norflurazon, acifluorfen, chloramben methyl ester, clopyralid,dicamba, picloram, dinoseb, DNOC, chlorothalonil, dichlobenil,2,6-dichlorobenzamide (BAM), triclopyr, bromoxynil, bromacil, terbacil,fenuron, fluometuron, linuron, neburon, dalapon, diquat, endothall,Glyphosate, N-dealkylated triazines, mecoprop Industrial chromatedcopper arsenate, Carbon tetrachloride, Chlorobenzene, p- material/wasteDichlorobenzene, 1,2-Dichloroethanem, 1,1-Dichloroethylene, cis-1,2-Dichloroethylene, trans-1,2-Dichloroethylene, Dichloromethane, Di(2-ethylhexyl) adipate, Di(2-ethylhexyl) phthalate, Dibutyl phthalate(DBP), diethyl phthalate (DEP), dicyclohexyl phthalate (DCHP), Dioxin(2,3,7,8-TCDD), Epichlorohydrin, Ethylene dibromide, Polychlorinatedbiphenyls, Pentachlorophenol, styrene, Tetrachloroethylene, Toluenediisocyanate (TDI), 1,2,4-Trichlorobenzene, 1,1,1-Trichloroethane,1,1,2-Trichloroethane, Trichloroethylene, perchloroethylene, Vinylchloride, Xylenes, alkylphenol (AP), AP + APE, bisphenol A (BPA),benzene, Xylene, Toluene, Styrene, Toluidine, 2-(p-Tolyl)ethylamine,Ethylbenzene, 2-Methyl-naphthalene, and Propyl-benzene, PAH (polynucleararomatic hydrocarbons) Drinking water Bromate, Chlorite, Haloaceticacids, Total Trihalomethanes, Chloramines, Chlorine, Chlorine dioxide,Benzo(a)pyrene, 4-tert-octylphenol Household Acrylamide, linearalkylbenzene sulfonates (LAS), alkyl ethoxylates (AE), waste/Sewagealkylphenol ethoxylates (APE), triclosan runoff Poison/toxinsN-methylamino-L-alanine (BMAA), Clostridium botulinum neurotoxins, BoNTA, B, D, E, Ricin A, B, tetanus toxin, diphtheria toxin, pertussis toxinHeavy metal mercury/methylmercury, lead/tetraethyl lead, zinc, copper,nickel, cadmium, chromium(VI)/chromate, aluminum, iron, arsenic, cobalt,selenium, silver, antimony, thallium, polonium, radium, tin,metallothionein (in carp liver tissue) Other Lithium, beryllium,manganese, barium, cyanide, fluoride metals/inorganic chemicalsPathogens/microbes Anthrax (LF), Giardia lamblia, Legionella, TotalColiforms (including fecal (antigen in coliform and E. Coli), Viruses(enteric) stapylococci (e.g., Staphylococcus pretheses) epidermidis andStaphylococcus aureus (enterotoxin A, B, C, G, I, cells, TSST-1),Enterrococcus faecalis, Pseudomonas aeruginosa, Escherichia coli(Shiga-like toxin, F4, F5, H, K, O, bacteriophage K1, K5, K13), othergram- positive bacteria, and gram-negative bacilli. Clostridiumdifficile (Toxin A, B) Bacteroidetes, Cryptosporidium parvum (GP900, p68or cryptopain, oocyst), Candida albicans Bacillus anthracis, Bacillusstearothermophilus Norovirus, Listeria monocytogenes (internalin),Leptospira interrogans, Leptospira biflexa, Clostridium perfringens(Epsilon toxin), Salmonella typhimurium, Yersinia pestis (F1, Vantigens), Aspergillus flavus (aflatoxin), Aspergillus parasiticus(aflatoxin), avian influenza virus, Ebola virus (GP), Histoplasmacapsulatum, Blastomyces dermatitidis (A antigen) Gram-positive bacteria(teichoic acid), Gram-ngative bacteria (such as Pseudomonas aeruginosa,Klebsiella pneumoniae, Salmonella enteriditis, Enterobacter aerogenes,Enterobacter hermanii, Yersinia enterocolitica and Shigellasonnei)(LPS), Polio virus, Influenza type A virus Disease specific prion(PrP-d) Allergens mite (Acas13, Blot1, Blot3, Blot4, Blot5, Blot6,Blot10, Blot11, Blot12, Blot13, Blot19); American house dust mite(Derf1, Derf2, Derf3, Derf7, Derf10, Derf11, Derf14, Derf15, Derf16,Derf17, Derf18w); house dust mite (Derm1); European house dust mite(Derp1, Derp2, Derp3, Derp4, Derp5, Derp6, Derp7, Derp8, Derp9, Derp10,Derp11, Derp14, Derp20, Derp21); mite (Eurm2; Eurm14); storage mite(Glyd2, Lepd2, Lepd5, Lepd7, Lepd10, Lepd13, Tyrp2, Tyrp13);Dermatophagoides farinae (Derf1.0101, Derf1.0102, Derf1.0103,Derf1.0104, Derf1.0105, Derf2.0101, Derf2.0102, Derf2.0103, Derf2.0104,Derf2.0105, Derf2.0106, Derf2.0107, Derf2.0108, Derf2.0109, Derf2.0110,Derf2.0111, Derf2.0112, Derf2.0113, Derf2.0114, Derf2.0115, Derf2.0116,Derf2.0117); Dermatophagoides pteronyssinus (Derp1.0101, Derp1.0102,Derp1.0103, Derp1.0104, Derp1.0105, Derp1.0106, Derp1.0107, Derp1.0108,Derp1.0109, Derp1.0110, Derp1.0111, Derp1.0112, Derp1.0113, Derp1.0114,Derp1.0115, Derp1.0116, Derp1.0117, Derp1.0118, Derp1.0119, Derp1.0120,Derp1.0121, Derp1.0122, Derp1.0123, Derp2.0101, Derp2.0102, Derp2.0103,Derp2.0104, Derp2.0105, Derp2.0106, Derp2.0107, Derp2.0108, Derp2.0109,Derp2.0110, Derp2.0111, Derp2.0112, Derp2.0113); Euroglyphus maynei(Eurm2.0101, Eurm2.0102); Glycyphagus domesticus (Glyd2.0101,Glyd2.0201); and Lepidoglyphus destructor (Lepd2.0101, Lepd2.0101,Lepd2.0101, Lepd2.0102, Lepd2.0201, Lepd2.0202) Pollen (Short Ragweed(Ambrosia artemisiifolia) allergen, Amb a 1, Amba2, Amba3, Amba5, Amba6,Amba7, Amba8, Amba9, Arnba10; Betula verrucosa allergen, Bet v 1, Phleumpratense allergen, Phl p 5), giant ragweed (Ambt5); mugwort (Artv1,Artv2, Artv3, Artv4, Artv5, Artv6); sunflower (Hela1, Hela2, Hela3);Mercurialis annua (Mera1); lamb's-quarters, pigweed (Chea1); whitegoosefoot (Chea2, Chea3); Russian-thistle (Salk1); Rosy periwinkle(Catr1); English plantain (Plal1); Japanese hop (Humj1); Parietariajudaica (Parj1, Parj2, Parj3); Parietaria officinalis (Paro1); Ambrosiaartemisiifolia (Amba8.0101, Amba8.0102, Amba9.0101, Amba9.0102);Plantago lanceolata (Plal1.0101, Plal1.0102, Plal1.0103); and Parietariajudaica (Parj1.0101, Parj1.0102, Parj1.0201, Par2.0101, Parj2.0102,Parj3.0101, Parj3.0102), Bermuda grass (Cynd1, Cynd7, Cynd12, Cynd15,Cynd22w, Cynd23, Cynd24); orchard grass (Dacg1, Dacg2, Dacg3, Dacg5);meadow fescue (Fesp4w); velvet grass (HolH); rye grass (Lolp1, Lolp2,Lolp3, Lolp5, Lolp11); canary grass (Phaa1); Timothy (Phlp1, Phlp2,Phlp4, Phlp5, Phlp6, Phlp11, Phlp12, Phlp13); Kentucky blue grass(Poap1, Poap5); Johnson grass (Sorh1); Cynodon dactylon (Cynd1.0101,Cynd1.0102, Cynd1.0103, Cynd1.0104, Cynd1.0105, Cynd1.0106, Cynd1.0107,Cynd1.0201, Cynd1.0202, Cynd1.0203, Cynd1.0204); Holcus lanatus(Holl1.0101, Holl1.0102); Lolium perenne (Lolp1.0101, Lolp1.0102,Lolp1.0103, Lolp5.0101, Lolp5.0102); Phleum pretense (Phlp1.0101,Phlp1.0102, Phlp4.0101, Phlp4.0201, Phlp5.0101, Phlp5.0102, Phlp5.0103,Phlp5.0104, Phlp5.0105, Phlp5.0106, Phlp5.0107, Phlp5.0108, Phlp5.0201,Phlp5.0202); and Secale cereale (Secc20.0101, Secc20.0201), Alder(Alng1); Birch (Betv1, Betv2, Betv3, Betv4, Betv6, Betv7); hornbeam(Carb1); chestnut (Cass1, Cass5, Cass8); hazel (Cora1, Cora2, Cora8,Cora9, Coral0, Cora11); White oak (Quea1); Ash (Frae1); privet (Ligv1);olive (Olee1, Olee2, Olee3, Olee4, Olee5, Olee6, Olee7, Olee8, Olee9,Olee10); Lilac (Syrv1); Sugi (Cryj1, Cryj2); cypress (Cupa1); commoncypress (Cups1, Cups3w); mountain cedar (Juna1, Juna2, Juna3); pricklyjuniper (Juno4); mountain cedar (Juns1); eastern red cedar (Junv1);London plane tree (Plaa1, Plaa2, Plaa3); date palm (Phod2); Betulaverrucosa (Betv1.0101, Betv1.0102, Betv1.0103, Betv1.0201, Betv1.0301,Betv1.0401, Betv1.0402, Betv1.0501, Betv1.0601, Betv1.0602, Betv1.0701,Betv1.0801, Betv1.0901, Betv1.1001, Betv1.1101, Betv1.1201, Betv1.1301,Betv1.1401, Betv1.1402, Betv1.1501, Betv1.1502, Betv1.1601, Betv1.1701,Betv1.1801, Betv1.1901, Betv1.2001, Betv1.2101, Betv1.2201, Betv1.2301,Betv1.2401, Betv1.2501, Betv1.2601, Betv1.2701, Betv1.2801, Betv1.2901,Betv1.3001, Betv1.3101, Betv6.0101, Betv6.0102); Carpinus betulus(Carb1.0101, Carb1.0102, Carb1.0103, Carb1.0104, Carb1.0105, Carb1.0106,Carb1.0106, Carb1.0106, Carb1.0106, Carb1.0107, Carb1.0107, Carb1.0108,Carb1.0201, Carb1.0301, Carb1.0302); Corylus avellana (Cora1.0101,Cora1.0102, Cora1.0103, Cora1.0104, Cora1.0201, Cora1.0301, Cora1.0401,Cora1.0402, Cora1.0403, Cora1.0404); Ligustrum vulgare (Ligv1.0101,Ligv1.01.02); Olea europea (Olee1.0101, Olee1.0102, Olee1.0103,Olee1.0104, Olee1.0105, Olee1.0106, Olee1.0107); Syringa vulgaris(Syrv1.0101, Syrv1.0102, Syrv1.0103); Cryptomeria japonica (Cryj2.0101,Cryj2.0102); and Cupressus sempervirens (Cups1.0101, Cups1.0102,Cups1.0103, Cups1.0104, Cups1.0105) mold (Alternaria alternata allergen,Alt a 1, Alta3, Alta4, Alta5, Alta6, Alta7, Alta8, Alta10, Alta12,Alta13, Aspergillus fumigatus allergen, Asp f 1, Aspf2, Aspf3, Aspf4,Aspf5, Aspf6, Aspf7, Aspf8, Aspf9, Aspf10, Aspf11, Aspf12, Aspf13,Aspf15, Aspf16, Aspf17, Aspf18, Aspf22w, Aspf23, Aspf27, Aspf28,Aspf29); Aspergillus niger (Aspn14, Aspn18, Aspn25); Aspergillus oryzae(Aspo13, Aspo21); Penicillium brevicompactum (Penb13, Penb26);Penicillium chrysogenum (Pench13, Pench18, Pench20); Penicilliumcitrinum (Penc3, Penc13, Penc19, Penc22w, Penc24); Penicillium oxalicum(Peno18); Fusarium culmorum (Fuse1, Fusc2); Trichophyton rubrum (Trir2,Trir4); Trichophyton tonsurans (Trit1, Trit4); Candida albicans (Canda1,Canda3); Candida boidinii (Candb2); Psilocybe cubensis (Psic1, Psic2);shaggy cap (Copd, Copc2, Copc3, Copc5, Copc7); Rhodotorula mucilaginosa(Rhom1, Rhom2); Malassezia furfur (Malaf2, Malaf3, Malaf4); Malasseziasympodialis (Malas1, Malas5, Malas6, Malas7, Malas8, Malas9, Malas10,Malas11, Malas12, Malas13); Epicoccum purpurascens (Epip1); andAlternaria alternate (Alta1.0101, Alta1.0102), Aspergillus versicolorantigen, S. chartarum antigen), Cladosporium herbarum (Clah2, Clah5,Clah6, Clah7, Clah8, Clah9, Clah10, Clah12); Aspergillus flavus(Aspf113); animals (Bos domesticus dander allergen, Bos d 2, Bosd3,Bosd4, Bosd5, Bosd6, Bosd7, Bosd8, Bosd2.0101, Bosd2.0102, Bosd2.0103,Canis familiaris allergen, Can f 1, Canf2, Canf3, Canf4, Equus caballusallergen, Equc1, Equc2, Equc3, Equc4, Equc5, Felis domesticus allergen,Fel d 1, Feld2, Feld3, Feld4, Feld5w, Feld6w, Feld7w, guinea pig (Cavp1,Cavp2); Mouse Urinary Protein (MUP, Musm1) allergen, Mus m 1, RatUrinary Protein (RUP, Ratn1) allergen, Rat n 1., Equus caballus(Equc2.0101, Equc2.0102)) Mosquito (Aeda1, Aeda2); honey bee (Apim1,Apim2, Apim4, Apim6, Apim7); bumble bee (Bomp1, Bomp4); German cockroach(Blag1, Blag2, Blag4, Blag5, Blag6, Blag7, Blag8); American cockroach(Pera1, Pera3, Pera6, Pera7); midge (Chit1-9, Chit1.01, Chit1.02,Chit2.0101, Chit2.0102, Chit3, Chit4, Chit5, Chit6.01, Chit6.02, Chit7,Chit8, Chit9); cat flea (Ctef1, Ctef2, Ctef3); pine processionary moth(Thap1); silverfish (Leps1); white face hornet (Dolm1, Dolm2, Dolm5);yellow hornet (Dola5); wasp (Pola1, Pola2, Pola5, Pole1, Pole5, Polf5,Polg5, Polm5, Vesvi5); Mediterranean paper wasp (Pold1, Pold4, Pold5);European hornet (Vespc1, Vespc5); giant asian hornet (Vespm1, Vespm5);yellowjacket (Vesf5, Vesg5, Vesm1, Vesm2, Vesm5, Vesp5, Vess5, Vesv1,Vesv2, Vesv5); Australian jumper ant (Myrp1, Myrp2); tropical fire ant(Solg2, Solg4); fire ant (Soli2, Soli3, Soli4); Brazilian fire ant(Sols2); California kissing bug (Triap1); Blattella germanica(Blag1.0101, Blag1.0102, Blag1.0103, Blag1.02, Blag6.0101, Blag6.0201,Blag6.0301); Periplaneta Americana (Pera1.0101, Pera1.0102, Pera1.0103,Pera1.0104, Pera1.02, Pera3.01, Pera3.0201, Pera3.0202, Pera3.0203,Pera7.0101, Pera7.0102); Vespa crabo (Vespc5.0101, Vespc5.0101); andVespa mandarina (Vesp m 1.01, Vesp m 1.02) Nematode (Anis1, Anis2,Anis3, Anis4); pigeon tick (Argr1); worm (Ascs1); papaya (Carp1); softcoral (Denn1); rubber (latex)(Hevb1, Hevb2, Hevb3, Hevb4, Hevb5,Hevb6.01, Hevb6.02, Hevb6.03, Hevb7.01, Hevb7.02, Hevb8, Hevb9, Hevb10,Hevb11, Hevb12, Hevb13); human autoallergens (Homs1, Homs2, Homs3,Homs4, Homs5); obeche (Trips1); and Hevea brasiliensis (Hevb6.01,Hevb6.0201, Hevb6.0202, Hevb6.03, Hevb8.0101, Hevb8.0102, Hevb8.0201,Hevb8.0202, Hevb8.0203, Hevb8.0204, Hevb10.0101, Hevb10.0102,Hevb10.0103, Hevb11.0101, Hevb11.0102)

Foodstuff Testing.

As summarized above, the devices, systems and methods in the presentinvention can find use in analyzing a foodstuff sample, e.g., a samplefrom raw food, processed food, cooked food, drinking water, etc., forthe presence of foodstuff markers. A foodstuff marker can be anysuitable marker, such as those shown in Table B9, below, that can becaptured by a capturing agent that specifically binds the foodstuffmarker in a CROF device configured with the capturing agent. Theenvironmental sample can be obtained from any suitable source, such astap water, drinking water, prepared food, processed food or raw food,etc. In some embodiments, the presence or absence, or the quantitativelevel of the foodstuff marker in the sample can be indicative of thesafety or harmfulness to a subject if the food stuff is consumed. Insome embodiments, the foodstuff marker is a substance derived from apathogenic or microbial organism that is indicative of the presence ofthe organism in the foodstuff from which the sample was obtained. Insome embodiments, the foodstuff marker is a toxic or harmful substanceif consumed by a subject. In some embodiments, the foodstuff marker is abioactive compound that can unintentionally or unexpectedly alter thephysiology if consumed by the subject. In some embodiments, thefoodstuff marker is indicative of the manner in which the foodstuff wasobtained (grown, procured, caught, harvested, processed, cooked, etc.).In some embodiments, the foodstuff marker is indicative of thenutritional content of the foodstuff. In some embodiments, the foodstuffmarker is an allergen that can induce an allergic reaction if thefoodstuff from which the sample is obtained is consumed by a subject.

In some embodiments, the devices, systems and methods in the presentinvention further includes receiving or providing a report thatindicates the safety or harmfulness for a subject to consume the foodstuff from which the sample was obtained based on information includingthe measured level of the foodstuff marker. The information used toassess the safety of the foodstuff for consumption can include dataother than the type and measured amount of the foodstuff marker. Theseother data can include any health condition associated with the consumer(allergies, pregnancy, chronic or acute diseases, current prescriptionmedications, etc.).

The report can be generated by the device configured to read the CROFdevice, or can be generated at a remote location upon sending the dataincluding the measured amount of the foodstuff marker. In some cases, afood safety expert can be at the remote location or have access to thedata sent to the remote location, and can analyze or review the data togenerate the report. The food safety expert can be a scientist oradministrator at a governmental agency, such as the US Food and DrugAdministration (FDA) or the CDC, a research institution, such as auniversity, or a private company. In certain embodiments, the foodsafety expert can send to the user instructions or recommendations basedon the data transmitted by the device and/or analyzed at the remotelocation.

TABLE B9 Foodstuff Markers Source/Class Marker/target Pathogens/Bacillus anthracis (LF), Giardia lamblia, Legionella, Total Coliformsmicrobes (including fecal coliform and E. Coli), Viruses (enteric)stapylococci (e.g., Staphylococcus epidermidis and Staphylococcus aureus(enterotoxin A, B, C, G, I, cells, TSST-1), Enterrococcus faecalis,Pseudomonas aeruginosa, Escherichia coli (Shiga-like toxin, F4, F5, H,K, O, bacteriophage K1, K5, K13), other gram-positive bacteria, andgram-negative bacilli. Clostridium difficile (Toxin A, B),Bacteroidetes, Cryptosporidium parvum (GP900, p68 or cryptopain,oocyst), Candida albicans, Bacillus anthracis, Bacillusstearothermophilus, Bacillus cereus, Bacillus licheniformis, Bacillussubtilis, Bacillus pumilus, Bacillus badius, Bacillus globigii,Salmonella typhimurium, Escherichia coli O157:H7, Norovirus, Listeriamonocytogenes (internalin), Leptospira interrogans, Leptospira biflexa,Campylobacter jejuni, Campylobacter coli, Clostridium perfringens,Aspergillus flavus (aflatoxins), Aspergillus parasiticus (aflatoxins),Ebola virus (GP), Histoplasma capsulatum, Blastomyces dermatitidis (Aantigen), Gram-positive bacteria (teichoic acid), Gram-negative bacteria(such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonellaenteriditis, Enterobacter aerogenes, Enterobacter hermanii, Yersiniaenterocolitica and Shigella sonnei)(LPS), Polio virus, Influenza type Avirus, Disease specific prion (PrP-d), Hepatitis A virus, Toxoplasmagondii, Vibrio cholera, Vibrio parahaemolyticus, Vibrio vulnificus,Enterococcus faecalis, Enterococcus faecium Toxins/N-methylamino-L-alanine (BMAA), Clostridium botulinum neurotoxins,carcinogens BoNT A, B, Ricin A, B; diphtheria toxin; Aristolochic acid;Colchicine, Ochratoxin A, Sterigmatocystin, Ergotamine, Fumonisins,Fusarin C, domoic acid, Brevetoxin, Mycotoxins Halogenated Heptachlor,chlordane hydrocarbons Heavy metals Lead, mercury, cadmium Allergenspeanut (Ara h 1, Ara h 2, Ara h 6), fish, shellfish, mollusks, shrimp(D. pteronyssinus tropomyosin allergen, Der p 10) Cod (Gadc1); Atlanticsalmon (Sals1); domestic cattle milk (Bosd4, Bosd5, Bosd6, Bosd7,Bosd8); chicken/egg (Gald1, Gald2, Gald3, Gald4, Gald5); shrimp (Mete1);shrimp (Pena1, Peni1); black tiger shrimp (Penm1, Penm2); squid (Todp1),brown garden snail (Helas1); abalone (Halm1); edible frog (Rane1,Rane2); oriental mustard (Braj1); rapeseed (Bran1); cabbage (Brao3);turnip (Brar1, Brar2); barley (Horv15, Horv16, Horv17, Horv21); rye(Secc20); wheat (Tria18, Tria19, Tria25, Tria26, gliadin); corn (Zeam14,Zeam25); rice (Orys1), celery (Apig1, Apig4, Apig5); carrot (Dauc1,Dauc4); hazelnut (Cora1.04, Cora2, Cora8); strawberry (Fraa1, Fraa3,Fraa4); apple (Mald1, Mald2, Mald3, Mald4); pear (Pyrc1, Pyrc4, Pyrc5);avocado (Persa1); apricot (Pruar1, Pruar3); sweet cherry (Pruav1,Pruav2, Pruav3, Pruav4); European plum (Prud3); almond (Prudu4); peach(Prup3, Prup4); asparagus (Aspao1); saffron crocus (Cros1, Cros2);lettuce (Lacs1); grape (Vitv1); banana (Musxp1); pineapple (Anac1,Anac2); lemon (Citl3); sweet orange (Cits1, Cits2, Cits3); litchi(Litd); yellow mustard (Sinai); soybean (Glym1, Glym2, Glym3, Glym4);mung bean (Vigr1); peanut (Arah1, Arah2, Arah3, Arah4, Arah5, Arah6,Arah7, Arah8); lentil (Lenc1, Lenc2); pea (Piss1, Piss2); kiwi (Actc1,Actc2); bell pepper (Capa1w, Capa2); tomato (Lyce1, Lyce2, Lyce3);potato (Solat1, Solat2, Solat3, Solat4); Brazil nut (Bere1, Bere2);black walnut (Jugn1, Jugn2); English walnut (Jugr1, Jugr2, Jugr3);Cashew (Anao1, Anao2, Anao3); Castor bean (Ricc1); sesame (Sesi1, Sesi2,Sesi3, Sesi4, Sesi5, Sesi6); muskmelon (Cucm1, Cucm2, Cucm3);Chinese-date (Zizm1); Anacardium occidentale (Anao1.0101, Anao1.0102);Apium graveolens (Apig1.0101, Apig1.0201); Daucus carota (Dauc1.0101,Dauc1.0102, Dauc1.0103, Dauc1.0104, Dauc1.0105, Dauc1.0201); Citrussinensis (Cits3.0101, Cits3.0102); Glycine max (Glym1.0101, Glym1.0102,Glym3.0101, Glym3.0102); Lens culinaris (Lenc1.0101, Lenc1.0102,Lenc1.0103); Pisum sativum (Piss1.0101, Piss1.0102); Lycopersiconesculentum (Lyce2.0101, Lyce2.0102); Fragaria ananassa (Fraa3.0101,Fraa3.0102, Fraa3.0201, Fraa3.0202, Fraa3.0203, Fraa3.0204, Fraa3.0301);Malus domestica (Mald1.0101, Mald1.0102, Mald1.0103, Mald1.0104,Mald1.0105, Mald1.0106, Mald1.0107, Mald1.0108, Mald1.0109, Mald1.0201,Mald1.0202, Mald1.0203, Mald1.0204, Mald1.0205, Mald1.0206, Mald1.0207,Mald1.0208, Mald1.0301, Mald1.0302, Mald1.0303, Mald1.0304, Mald1.0401,Mald1.0402, Mald1.0403, Mald3.0101w, Mald3.0102w, Mald3.0201w,Mald3.0202w, Mald3.0203w, Mald4.0101, Mald4.0102, Mald4.0201,Mald4.0202, Mald4.0301, Mald4.0302); Prunus avium (Pruav1.0101,Pruav1.0201, Pruav1.0202, Pruav1.0203); and Prunus persica (Prup4.0101,Prup4.0201) Synthetic 17beta-estradiol (E2), estrone (EI), estrogen (ES:EI + E2 + estradiol (E3)), hormone 1 7alfa-ethynylestradiol (EE2),4-nonylphenpol, testosterone, analogues Diethylstilbestrol (DES),recombinant bovine growth hormone (rBGH) Pesticides Dieldrin, carbaryl,chlorpyrifos, parathion, aldrin, endosulfan I, endrin, toxaphene,O-ethyl O-4-nitrophenyl phenylphosphono-thioate (EPN), fenitrothion,pirimiphos-methyl, thiabendazole, methiocarb, Carbendazim, deltamethrin,Avermectin, Carbaryl, Cyanazine, Kresoxim, resmethrin, kadethrin,cyhalothrin, biphenthrin, fenpropathrin, allethrin and tralomethrin;aromatic-substituted alkanecarboxylic acid esters such as fenvarerate,flucythrinate, fluvalinate and cycloprothrin; and non-ester compoundssuch as etofenprox, halfenprox (MTI-732), 1-(3-phenoxyphenyl)-4-(4-ethoxyphenyl)-4-methylpentane (MTI-790), 1-(3-phenoxy-4-fluorophenyl)-4-(4-ethoxyphenyl)-4-methylpentane (MTI-800),dimethyl-(4-ethoxyphenyl)-(3-phenoxybenzyloxy)silane (SSI-116),silafluofen and PP-682, carbofuran, triazophos Herbicide atrazine,deethylatrazine, cyanazine, terbuthylazine, terbutryn, molinate,simazine, prometon, promteryn, hydroxyatrazine, 2,6-dichlorobenzamide(BAM), N-dealkylated triazines, mecoprop, thiram, acetochlor, alachlor,Chlorothalonil, Chlorsulfuron, Fenoxaprop ethyl, Linuron, monuron,diuron, Quizalofop-ethyl, Imazalil, Iprodione, Iprovalicarb,Myclobutanil Industrial Dioxin (2,3,7,8-TCDD), 4-tert-octylphenol,bisphenol A (BPA), Styrene, material/waste Di(2-ethylhexyl) phthalate,Dibutyl phthalate (DBP), benzophenone, benzene, trichloroethylene,polychlorinated biphenyl (PCB), nonylphenol, p- cresol, melamine, xyleneAntibiotics 3-Amino-5-morpholinomethyl-2-oxazolidone (AMOZ; tissue boundmetabolite of furaltadone), oxytetracycline, rolitetracycline,Actinomycin D, Amikacin sulfate, Aminoglycosides, nitrofuran (AOZ),Chloramphenicol, Doxycycline, Streptomycin, gentamicin, neomycin,kanamycin, sulfamethazine, enrofloxacin, sulfadiazine, enrofloxacin Foodcoloring/ Tartrazine, ethoxyquin, erythritol, penicillin,Fluoroquinolone, Malachite additive/ Green/Leucomalachite Green, C.I.Solvent Yellow 14 (Sudan I), preservative Food Acrylamide,2-amino-3-methylimidazo(4,5-f)quinolone, Benzo[a]pyrene preparationNutritional Vitamins A (retinol), B12 (cobalmins), B6 (pyridoxine), B1(thiamin), B2 content (riboflavin), B3 (niacin), B5 (D-pantothenicacid), B7 (biotin), B9 (folic acid), C, D, E (alpha-tocopherol); OtherCaffeine, Ovine myofibril proteins, Etodolac

TABLE B10 POC analytes Disease/Condition Analyte 1. Haematology Completeblood RBCs, WBCs, Platelets count (CBC) 2. Lipid panel Cholesterol levelTriglyceride, Total cholesterol, HDL cholesterol, LDL cholesterol 3.Urinalysis Renal Diseases/ pH, Protein, Glucose, Nitrites, Leukocyteesterase, Ketones, Blood cells, Kidney Function Casts, Crystals,Microorganisms, Squamous cells 4. Diabetes Diabetes Glucose, HbA1c,11-8, CTSS, ITGB2, HLA-DRA, CD53, PLAG27, or MMP9; RBP4;8-iso-prostaglandin F2α (8-iso-PGF2α), 11-dehydro- thromboxane B2 (TXM),C-peptide, Advanced glycosylation end products (AGEs),1,5-anhydroglucitol, NGPTL3 and 4, autoantibodies (Zn transporter 8,glutamic acid decarboxylase (GAD)), ATP-binding cassette, sub-family C(CFTR/MRP), member 8; ATP-binding cassette, sub-family C (CFTR/MRP),member 9; angiotensin I converting enzyme (peptidyl- dipeptidase A) 1;adenylate cyclase activating polypeptide 1 (pituitary); adiponectin, C1Qand collagen domain containing; adiponectin receptor 1; adiponectinreceptor 2; adrenomedullin; adrenergic, beta-2-, receptor, surface;advanced glycosylation end product-specific receptor; agouti relatedprotein homolog (mouse); angiotensinogen (serpin peptidase inhibitor,clade A, member 8); angiotensin II receptor, type 1; angiotensin IIreceptor-associated protein; alpha-2-HS-glycoprotein; v-akt murinethymoma viral oncogene homolog 1; v-akt murine thymoma viral oncogenehomolog 2; albumin; Alstrom syndrome 1; archidonate 12- lipoxygenase;ankyrin repeat domain 23; apelin, AGTRL 1 Ligand; apolipoprotein A-I;apolipoprotein A-II; apolipoprotein B (including Ag(x) antigen);apolipoprotein E; aryl hydrocarbon receptor nuclear translocator; Arylhydrocarbon receptor nuclear translocator-like; arrestin, beta 1;arginine vasopressin (neurophysin II, antidiuretic hormone, Diabetesinsipidus, neurohypophyseal); bombesin receptor subtype 3; betacellulin;benzodiazepine receptor (peripheral); complement component 3; complementcomponent 4A (Rodgers blood group); complement component 4B (Childoblood group); complement component 5; Calpain- 10; cholecystokinin;cholecystokinin (CCK)-A receptor; chemokine (C-C motif) ligand 2; CD14molecule; CD163 molecule; CD36 molecule (thrombospondin receptor); CD38molecule; CD3d molecule, delta (CD3- TCR complex); CD3g molecule, gamma(CD3-TCR complex); CD40 molecule, TNF receptor superfamily member 5;CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome); CD68molecule; cyclin- dependent kinase 5; complement factor D (adipsin);CASP8 and FADD- like apoptosis regulator; Clock homolog (mouse); chymase1, mast cell; cannabinoid receptor 1 (brain); cannabinoid receptor 2(macrophage); cortistatin; carnitine palmitoyltransferase I; carnitinepalmitoyltransferase II; complement component (3b/4b) receptor 1;complement component (3d/Epstein Barr virus) receptor 2; CREB bindingprotein (Rubinstein- Taybi syndrome); C-reactive protein,pentraxin-related; CREB regulated transcription coactivator 2; colonystimulating factor 1 (macrophage); cathepsin B; cathepsin L; cytochromeP450, family 19, subfamily A, polypeptide 1; Dio-2, deathinducer-obliterator 1; dipeptidyl-peptidase 4 (CD26, adenosine deaminasecomplexing protein 2); epidermal growth factor (beta-urogastrone); earlygrowth response 1; epididymal sperm binding protein 1; ectonucleotide;pyrophosphatase/phosphodiesterase 1; E1A binding protein p300;coagulation factor XIII, A1 polypeptide; coagulation factor VIII,procoagulant component (hemophilia A); fatty acid binding protein 4,adipocyte; Fas (TNF receptor superfamily, member 6); Fas ligand (TNFsuperfamily, member 6); free fatty acid receptor 1; fibrinogen alphachain; forkhead box A2; forkhead box O1A; ferritin; glutamatedecarboxylase 2; galanin; gastrin; glucagon; glucokinase;gamma-glutamyltransferase 1; growth hormone 1; ghrelin/obestatinpreprohormone; gastric inhibitory polypeptide; gastric inhibitorypolypeptide receptor; glucagon-like peptide 1 receptor; guaninenucleotide binding protein (G protein), beta polypeptide 3;glutamic-pyruvate transaminase (alanine aminotransferase); gastrinreleasing peptide (bombesin); gelsolin (amyloidosis, Finnish type);hemoglobin; hemoglobin, beta; hypocretin (orexin); neuropeptide;precursor; hepatocyte growth factor (hepapoietin A; scatter factor);hepatocyte nuclear factor 4, alpha; haptoglobin; hydroxysteroid(11-beta); dehydrogenase 1; heat shock 70 kDa protein 1B; islet amyloidpolypeptide; intercellular adhesion molecule 1 (CD54), human rhinovirusreceptor; interferon, gamma; insulin-like growth factor 1 (somatomedinC); insulin-like growth factor 2 (somatomedin A); insulin-like growthfactor binding protein 1; insulin-like growth factor binding protein 3;inhibitor of kappa light polypeptide gene enhancer in B-cells, kinasebeta; interleukin 10; interleukin 18 (interferon-gamma-inducing factor);interleukin 1, alpha; interleukin 1, beta; interleukin 1 receptorantagonist; interleukin 2; interleukin 6 (interferon, beta 2);interleukin 6 receptor; interleukin 8; inhibin, beta A (activin A,activin AB alpha polypeptide); insulin; insulin receptor; insulinpromoter factor-1; insulin receptor substrate 1; insulin receptorsubstrate-2; potassium inwardly-rectifying channel, subfamily J, member11; potassium inwardly-rectifying channel, subfamily J, member 8;klotho; kallikrein B, plasma (Fletcher factor) 1; leptin (obesityhomolog, mouse); leptin receptor; legumain; lipoprotein, Lp(a);lipoprotein lipase; v- maf musculoaponeurotic brosarcoma oncogenehomolog A (avian); mitogen-activated protein kinase 8; interactingprotein 1; mannose-binding lectin (protein C) 2, soluble (opsonicdefect); melanocortin 4 receptor; melanin-concentrating hormone receptor1; matrix metallopeptidase 12 (macrophage elastase); matrixmetallopeptidase 14 (membrane-inserted); matrix metallopeptidase 2(gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase); matrixmetallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa type IVcollagenase); nuclear receptor co-repressor 1; neurogenicdifferentiation 1; nuclear factor of kappa light polypeptide geneenhancer in B-cells 1(p105); nerve growth factor, beta polypeptide; non-insulin-dependent Diabetes Mellitus (common, type 2) 1; non-insulin-dependent Diabetes Mellitus (common, type 2) 2; Noninsulin-dependentDiabetes Mellitus 3; nischarin (imidazoline receptor); NF-kappaBrepressing factor; neuronatin; nitric oxide synthase 2A; Niemann-Pickdisease, type C2; natriuretic peptide precursor B; nuclear receptorsubfamily 1, group D, member 1; nuclear respiratory factor 1; oxytocin,prepro-(neurophysin I); purinergic receptor P2Y, G-protein coupled, 10;purinergic receptor P2Y, G-protein coupled, 12; purinergic receptor P2Y,G-protein coupled, 2; progestagen-associated endometrial; protein(placental protein 14, pregnancy-associated endometrialalpha-2-globulin, alpha uterine protein); paired box gene 4; pre-B-cellcolony enhancing factor 1; phosphoenolpyruvate carboxykinase 1 (PEPCK1);proprotein convertase; subtilisin/kexin type 1; placental growth factor,vascular; endothelial growth factor-related protein;phosphoinositide-3-kinase, catalytic, alpha polypeptide;phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha);phospholipase A2, group XIIA; phospholipase A2, group IID; plasminogenactivator, tissue; patatin-like phospholipase domain containing 2;proopiomelanocortin (adrenocorticotropin/beta-lipotropin/alpha-melanocyte stimulating hormone/beta- melanocytestimulating hormone/beta-endorphin); paraoxonase 1 ESA, PON,Paraoxonase; peroxisome proliferative activated receptor, alpha;peroxisome proliferative activated receptor, delta; peroxisomeproliferative activated receptor, gamma; peroxisome proliferativeactivated receptor, gamma, coactivator 1; protein phosphatase 1,regulatory (inhibitor) subunit 3A (glycogen and sarcoplasmic reticulumbinding subunit, skeletal muscle); protein phosphatase 2A, regulatorysubunit B′(PR 53); protein kinase, AMP-activated, beta 1 non-catalyticsubunit; protein kinase, cAMP-dependent, catalytic, alpha; proteinkinase C, epsilon; proteasome (prosome, macropain) 26S subunit,non-ATPase, 9 (Bridge-1); prostaglandin E synthase;prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase andcyclooxygenase); protein tyrosine phosphatase, mitochondrial 1; PeptideYY retinol binding protein 4, plasma (RBP4); regenerating islet-derived1 alpha (pancreatic stone protein, pancreatic thread protein); resistin;ribosomal protein S6 kinase, 90 kDa, polypeptide 1; Ras-relatedassociated with Diabetes; serum amyloid A1; selectin E (endothelialadhesion molecule 1); serpin peptidase inhibitor, clade A (alpha-1antiproteinase, antitrypsin), member 6; serpin peptidase inhibitor,clade E (nexin, plasminogen activator inhibitor type 1), member 1;serum/glucocorticoid regulated kinase; sex hormone-binding globulin;thioredoxin interacting protein; solute carrier family 2, member 10;solute carrier family 2, member 2; solute carrier family 2, member 4;solute carrier family 7 (cationic amino acid transporter, y+ system),member 1(ERR); SNF1-like kinase 2; suppressor of cytokine signaling 3;v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian);sterol regulatory element binding transcription factor 1; solute carrierfamily 2, member 4; somatostatin receptor 2; somatostatin receptor 5;transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1);transcription factor 2, hepatic, LF-B3, variant hepatic nuclear factor;transcription factor 7-like 2 (T-cell specific, HMG- box); transforminggrowth factor, beta 1 (Camurati-Engelmann disease); transglutaminase 2(C polypeptide, protein-glutamine-gamma- glutamyltransferase);thrombospondin 1; thrombospondin, type I, domain containing 1; tumornecrosis factor (TNF superfamily, member 2); tumor necrosis factor (TNFsuperfamily, member 2); tumor necrosis factor receptor superfamily,member 1A; tumor necrosis factor receptor superfamily, member 1B;tryptophan hydroxylase 2; thyrotropin-releasing hormone; transientreceptor potential cation channe1, subfamily V, member 1; thioredoxininteracting protein; thioredoxin reductase 2; urocortin 3 (stresscopin);uncoupling protein 2 (mitochondria1, proton carrier); upstreamtranscription factor 1; urotensin 2; vascular cell adhesion molecule 1;vascular endothelial growth factor; vimentin; vasoactive intestinalpeptide; vasoactive intestinal peptide receptor 1; vasoactive intestinalpeptide receptor 2; von Willebrand factor; Wolfram syndrome 1(wolframin); X-ray repair complementing defective repair in Chinesehamster cells 6; c-peptide; cortisol; vitamin D3; estrogen; estradiol;digitalis-like factor; oxyntomodulin; dehydroepiandrosterone sulfate(DHEAS); serotonin (5-hydroxytryptamine); anti-CD38 autoantibodies;gad65 autoantibody; Angiogenin, ribonuclease, RNase A family, 5;Hemoglobin A1c; Intercellular adhesion molecule 3 (CD50); interleukin 6signal transducer (gp130, oncostatin M receptor); selectin P (granuleembrane protein 140 kDa, antigen CD62); TIMP metallopeptidase inhibitor;Proinsulin; endoglin; interleukin 2 receptor, beta; insulin-like growthfactor binding protein 2; insulin-like growth factor 1 receptor;fructosamine, N-acetyl-beta-d- glucosaminidase, pentosidine, advancedglycation end product, beta2- microglobulin, pyrraline 5. SexuallyTransmitted Diseases Chlamydia bacteria Chlamydia trachomatis Gonorrheabacteria Neisseria gonorrhoeae Syphilis Antibodies, bacterial DNATrichomonas protzoan Trichomoniasis Human DNA or RNA of HPV viruspapillomavirus (HPV) Genital herpes Antibodies Human HIV antigen p24,Antibodies Immunodeficiency Virus (HIV) 6. Other Infectious DiseasesEbola Antigen, IgM and IgG antibodies, RNA Malaria Antigen, Nucleicacids, Antibodies Hepatitis B and Viral proteins, Antibodies, Viral DNAHepatitis C Influenza Viral proteins, Antibodies, Viral DNA 7. Cardiactesting Cardiac markers Troponin (I or T), Creatine Kinase (CK) andCK-MB, Myoglobin, hs-CRP, BNP and NT-proBNP 8. Female Reproductiontesting Pregnancy test HCG (human chorionic gonadotropin) Ovulation testLH (luteinizing hormone) 9. Drugs of Abuse Alcohol Ethanol, ethylglucuronide Cocaine Cocaine, Benzolecgonine, Ecgonine, Ecgonine MethylEster Heroine Heroine, 6MAM, Morphine PCP PCP, PhencyclidineThienylcyclohexylpiperidine (TCP) Amphetamines Amphetamines (such asD-Amphetamine, D-Methamphetamine, L- Amphetamine, L-Methamphetamine,3,4-Methylenedioxy- methamphetamine (MDMA),3,4-Methylenedioxyamphetamine (MDA), 3,4-Methylenedioxyethylamphetamine(MDEA), Paramethoxyamphetamine (PMA)) Methamphetamine D-Methamphetamine,D-Amphetamine, L-Methamphetamine, Chloroquine, (+/−) Ephedrine,3,4-Methylenedioxy-methamphetamine (MDMA), 3,4-Methylenedioxyamphetamine(MDA), 3,4- Methylenedioxyethylamphetamine (MDEA), Procaine MDMA(Ecstasy) MDMA, MDA, MDEA, D-Amphetamine, D-Methamphetamine,Paramethoxyamphetamine (PMA) Barbiturates Secobarbital, Phenobarbital,Butalbital, Allobarbital, Alphenal, Amorbarbital, Aprobarbital,Hexobarbital, Butabarbital, Pentobarbital Phenobarbital Phenobarbital,Butalbital, Amobarbital, Secobarbital Benzodiazepines Oxazepam,Alprazolam, Bromazepam, Chlordiazepoxide, Clobazam, Clonazepam,Clorazepate, Delorazepam, Desalkyflurazepam, Diazepam, Estazolam,Fentanyl, Flunitrazepam (Rohypnol ®), Flurazepam, a- Hydroxyalprazolam,Lorazepam (Ativan ®), Lormetazepam, Medazepam, Midazolam, Nitrazepam,Nordiazepam, Prazepam, Temazepam, Tetrazepam Cannabis Δ9-THC,11-Nor-Δ8-THC-9-COOH, 11-Nor-Δ9-THC-9-COOH, 11- (Marijuana, etc.)Hydroxy-Δ9-tetrahydrocannabinol, Δ8-Tetrahydrocannabinol, Δ9-Tetrahydrocannabinol, Cannabinol, Cannabidiol, pentanoic acid, butanoicacid, 4-hydroxybutyl, 4-hydroxypentyl Codeine Morphine, Codeine,Diacetyl morphine (heroine), Ethylmorphine, Hydromorphone, Meperidine,6-Monoacetylmorphine, Morphine-3- glucuronide, Oxycodone, Oxymorphone,Promethazine, Rifampicine, Thebaine, Trimipamine Nicotine/CotinineCotinine, Nicotine Morphine Morphine Tricyclic Nortriptyline,Amitriptyline, Chlorpromazine, Clomipramine, antidepressantsCyclobenzaprine, Desipramine, Diphenyldramine, Doxepine, Imipramine,(TCA's) Nordoxepine, Opipramol, Protriptyline, Perphenazine, Promazine,Promethazine, Trimipramine LSD LSD Methadone EDDP, Doxylamine,Methadone, Methadol Methaqualone Methaqualone, 3-hydroxy methaqualone,4-hydroxy methaqualone, 2- hydroxy methaqualone, Amitriptyline,Carbamazepine, Nortriptyline, Phenytoin, Primidone, Theophylinebuprenorphine Buprenorphine, Buprenorphine-3-B-d-gluconoride,Nor-Buprenorphine, Nor-Buprenorphine-3-B-d-gluconoride KetamineKetamine, Norketamine, Dextromethorphan, Dextrorphantartrate, EDDP,Phencyclidine, Promazine, Meperidine, D-Methamphetamine, Mephentermineh.s., MDEA, Nordoxepin hydrochloride, Promethazine, D- Norpropoxyphene,Methadone MethCathinone MethCathinone, 4-MMC (Mephedrone), 3-MMC(3-methylmethcathinone), 4-MEC (4-methylethcathinone), Methylone (MDMC,bk-MDMA), Cathinone, MDPV MDPV MDPV, Cathinone, MethCathinonemethylphenidate methylphenidate tramadol Tramadol, N-demethyl-tramadol,O-demethyl-tramadol oxycodone Oxycodone, Oxymorphone, Codeine, DiacetylMorphine (Heroine), Ethylmorphine, Hydrocodone, Hydromorphone,Merperidine, 6- Monoacetylmorphine, Morphine,Morphine-3-beta-D-glucuronide, Thebaine propoxyphene D-propoxyphene,D-norpropoxyphene Fentanyl Methaqualone, Mecloqualone, 3-hydroxymethaqualone, 4-hydroxy methaqualone, 2-hydroxy methaqualone,Amitriptyline, Carbamazepine, Nortriptyline, Phenytoin, Primidone,Theophyline 10. Coagulation Disorders Congenital Platelet, Fibronogen,Factor V, Anti-Xa, Factor XIII screen, D-dimer hemophilia; VonWillebrand disease; Acquired hemophilia 11. Fecal Occult Blood TestColon Cancer; Blood cells, Hemoglobin, Fecal DNA colon polyps; crohn'sdisease; hemorrhoids; anal fissures; intestinal infections; Ulcers;Ulcerative colitis 12. Blood Gas and Electrolytes pH, pCO₂, pO₂, Sodium(Na+), Potassium (K+), Calcium (Ca++), HCO3, TCO2, SBE

The health conditions that can be diagnosed or measured by the subjectmethod, device and system include, but are not limited to: chemicalbalance; nutritional health; exercise; fatigue; sleep; stress;prediabetes; allergies; aging; exposure to environmental toxins,pesticides, herbicides, synthetic hormone analogs; pregnancy; menopause;and andropause.

In certain embodiments, relative levels of nucleic acids in two or moredifferent nucleic acid samples can be obtained using the above methods,and compared. In these embodiments, the results obtained from theabove-described methods are usually normalized to the total amount ofnucleic acids in the sample (e.g., constitutive RNAs), and compared.This can be done by comparing ratios, or by any other means. Inparticular embodiments, the nucleic acid profiles of two or moredifferent samples can be compared to identify nucleic acids that areassociated with a particular disease or condition.

In some examples, the different samples can consist of an “experimental”sample, i.e., a sample of interest, and a “control” sample to which theexperimental sample can be compared. In many embodiments, the differentsamples are pairs of cell types or fractions thereof, one cell typebeing a cell type of interest, e.g., an abnormal cell, and the other acontrol, e.g., normal, cell. If two fractions of cells are compared, thefractions are usually the same fraction from each of the two cells. Incertain embodiments, however, two fractions of the same cell can becompared. Exemplary cell type pairs include, for example, cells isolatedfrom a tissue biopsy (e.g., from a tissue having a disease such ascolon, breast, prostate, lung, skin cancer, or infected with a pathogenetc.) and normal cells from the same tissue, usually from the samepatient; cells grown in tissue culture that are immortal (e.g., cellswith a proliferative mutation or an immortalizing transgene), infectedwith a pathogen, or treated (e.g., with environmental or chemical agentssuch as peptides, hormones, altered temperature, growth condition,physical stress, cellular transformation, etc.), and a normal cell(e.g., a cell that is otherwise identical to the experimental cellexcept that it is not immortal, infected, or treated, etc.); a cellisolated from a mammal with a cancer, a disease, a geriatric mammal, ora mammal exposed to a condition, and a cell from a mammal of the samespecies, preferably from the same family, that is healthy or young; anddifferentiated cells and non-differentiated cells from the same mammal(e.g., one cell being the progenitor of the other in a mammal, forexample). In one embodiment, cells of different types, e.g., neuronaland non-neuronal cells, or cells of different status (e.g., before andafter a stimulus on the cells) can be employed. In another embodiment ofthe invention, the experimental material is cells susceptible toinfection by a pathogen such as a virus, e.g., human immunodeficiencyvirus (HIV), etc., and the control material is cells resistant toinfection by the pathogen. In another embodiment of the invention, thesample pair is represented by undifferentiated cells, e.g., stem cells,and differentiated cells.

7. Control and Measure the Sample Thickness without Using Spacers

In some embodiments of the present invention, the spacers that are usedto regulate the sample or a relevant volume of the sample are replacedby (a) positioning sensors that can measure the plate inner spacing, and(b) the devices that can control the plate positions and move the platesinto a desired plate inner spacing based on the information provided thesensors. In some embodiment, all the spacers are replaced by translationstage, monitoring sensors and feedback system.

Measuring of Spacing and/or Sample Thickness Using Optical Method.

In some embodiments, the measuring (f) of the spacing between the innersurfaces comprises the use of optical interference. The opticalinterference can use multiple wavelength. For example, the light signaldue to the interference of a light reflected at the inner surface of thefirst plate and the second plate oscillate with the wavelength of thelight. From the oscillation, one can determine the spacing between theinner surfaces. To enhance the interference signal, one of the innersurfaces or both can be coated with light reflection material.

In some embodiments, the measuring (f) of the spacing between the innersurfaces comprises taking optical imaging (e.g. taking a 2D(two-dimensional)/3D (three-dimensional) image of the sample and theimage taking can be multiple times with different viewing angles,different wavelength, different phase, and/or different polarization)and image processing.

Measuring of Entire Sample Area or Volume Using Optical Methods.

In some embodiments, the measuring (f) of the entire sample area orvolume comprises taking optical imaging (e.g. taking a 2D(two-dimensional)/3D (three-dimensional) image of the sample and theimage taking can be multiple times with different viewing angles,different wavelength, different phase, and/or different polarization)and image processing. The sample area means the area in the directionapproximately parallel to the first plate and the second plate. The 3Dimaging can use the method of fringe projection profilometry (FPP),which is one of the most prevalent methods for acquiringthree-dimensional (3D) images of objects.

In some embodiments, the measuring of the sample area or volume byimaging comprises (a) calibration of the image scale by using a sampleof the known area or volume (e.g., The imager is a smartphone and thedimensions of the image taken by the phone can be calibrated bycomparing an image of the a sample of known dimension taken the samephone); (b) comparison of the image with the scale markers (rulers)placed on or near the first plate and second plate (discussed furtherherein), and (c) a combination of thereof.

As used herein, light can include visible light, ultraviolet light,infrared light, and/or near infrared light. Light can includewavelengths in the range from 20 nm to 20,000 nm.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise, e.g., when the word “single” isused. For example, reference to “an analyte” includes a single analyteand multiple analytes, reference to “a capture agent” includes a singlecapture agent and multiple capture agents, reference to “a detectionagent” includes a single detection agent and multiple detection agents,reference to “an agent” includes a single agent and multiple agents, andreference to “a camera” includes a single camera and multiple cameras.

As used herein, the terms “adapted” and “configured” mean that theelement, component, or other subject matter is designed and/or intendedto perform a given function. Thus, the use of the terms “adapted” and“configured” should not be construed to mean that a given element,component, or other subject matter is simply “capable of” performing agiven function. Similarly, subject matter that is recited as beingconfigured to perform a particular function can additionally oralternatively be described as being operative to perform that function.

As used herein, the phrase, “for example,” the phrase, “as an example,”and/or simply the terms “example” and “exemplary” when used withreference to one or more components, features, details, structures,embodiments, and/or methods according to the present disclosure, areintended to convey that the described component, feature, detail,structure, embodiment, and/or method is an illustrative, non-exclusiveexample of components, features, details, structures, embodiments,and/or methods according to the present disclosure. Thus, the describedcomponent, feature, detail, structure, embodiment, and/or method is notintended to be limiting, required, or exclusive/exhaustive; and othercomponents, features, details, structures, embodiments, and/or methods,including structurally and/or functionally similar and/or equivalentcomponents, features, details, structures, embodiments, and/or methods,are also within the scope of the present disclosure.

As used herein, the phrases “at least one of” and “one or more of,” inreference to a list of more than one entity, means any one or more ofthe entity in the list of entity, and is not limited to at least one ofeach and every entity specifically listed within the list of entity. Forexample, “at least one of A and B” (or, equivalently, “at least one of Aor B,” or, equivalently, “at least one of A and/or B”) may refer to Aalone, B alone, or the combination of A and B.

As used herein, the term “and/or” placed between a first entity and asecond entity means one of (1) the first entity, (2) the second entity,and (3) the first entity and the second entity. Multiple entity listedwith “and/or” should be construed in the same manner, i.e., “one ormore” of the entity so conjoined. Other entity may optionally be presentother than the entity specifically identified by the “and/or” clause,whether related or unrelated to those entity specifically identified.Thus, as a non-limiting example, a reference to “A and/or B,” when usedin conjunction with open-ended language such as “comprising” may refer,in some embodiments, to A only (optionally including entity other thanB); in certain embodiments, to B only (optionally including entity otherthan A); in yet certain embodiments, to both A and B (optionallyincluding other entity). These entity may refer to elements, actions,structures, steps, operations, values, and the like.

In the event that any patents, patent applications, or other referencesare incorporated by reference herein and (1) define a term in a mannerthat is inconsistent with and/or (2) are otherwise inconsistent with,either the non-incorporated portion of the present disclosure or any ofthe other incorporated references, the non-incorporated portion of thepresent disclosure shall control, and the term or incorporateddisclosure therein shall only control with respect to the reference inwhich the term is defined and/or the incorporated disclosure was presentoriginally.

It is believed that the following claims particularly point out certaincombinations and subcombinations that are directed to one of thedisclosed inventions and are novel and non-obvious. Inventions embodiedin other combinations and subcombinations of features, functions,elements and/or properties may be claimed through amendment of thepresent claims or presentation of new claims in this or a relatedapplication. Such amended or new claims, whether they are directed to adifferent invention or directed to the same invention, whetherdifferent, broader, narrower, or equal in scope to the original claims,are also regarded as included within the subject matter of theinventions of the present disclosure.

1. (canceled)
 2. A method of forming a thin fluidic sample layer with auniform predetermined thickness by pressing with an imprecise pressingforce, comprising: (a) providing a device comprising a first plate, asecond plate, and spacers, wherein: i. the plates are movable relativeto each other into different configurations; ii. one or both plates areflexible; iii. each of the plates comprises an inner surface that has asample contact area for contacting a fluidic sample containing or beingsuspected of containing an analyte; iv. each of the plates comprises, onits respective outer surface, a force area for applying an imprecisepressing force that forces the plates together; v. one or both of theplates comprise the spacers that are permanently fixed on the innersurface of a respective plate; vi. the spacers have a predeterminedsubstantially uniform height that is equal to or less than 200 microns,and a predetermined fixed inter-spacer-distance; vii. the fourth powerof the inter-spacer-distance (ISD) divided by the thickness (h) and theYoung's modulus (E) of the flexible plate (ISD⁴/(hE)) is 5×10⁶ um³/GPaor less; and viii. at least one of the spacers is inside the samplecontact area; (b) depositing the fluidic sample on one or both of theplates; when the plates are configured in an open configuration, whereinthe open configuration is a configuration in which the two plates arepartially or completely separated apart and the spacing between theplates is not regulated by the spacers; (c) after (b), applying animprecise force on the force areas to bring the two plates into a closedconfiguration, in which: at least a part of the sample is compressed bythe two plates into a layer of substantially uniform thickness, whereinthe uniform thickness of the layer is confined by the sample contactsurfaces of the plates and is regulated by the plates and the spacers.3. (canceled)
 4. (canceled)
 5. (canceled)
 6. (canceled)
 7. (canceled) 8.(canceled)
 9. The method of claim 2, further comprising a step of usingan area-determination device to determine the lateral area of therelevant volume of the sample in a closed configuration of the plates.10. The method of claim 9, wherein the area-determination devicecomprises a camera.
 11. The method of claim 2, wherein the imprecisionforce has a magnitude in the range of 1N to 20 N and/or a pressure in arange of 0.1 psi to 280 psi.
 12. The method of claim 9, wherein thearea-determination device comprises a camera and an area in the samplecontact area of a plate, and wherein the area is in contact with thesample.
 13. (canceled)
 14. (canceled)
 15. (canceled)
 16. The method ofclaim 2, wherein the imprecision force is in the range of 20 N to 200 N.17. The method of claim 2, wherein the device is further configured tohave, after the pressing force is removed, a sample thickness that issubstantially the same in thickness and uniformity as that when theforce is applied.
 18. The method of claim 2, wherein the imprecise forceis provided by human hand.
 19. The method of claim 2, wherein theimprecision force has a pressure in the range of 0.01 kg/cm² (centimetersquare) to 100 kg/cm².
 20. The method of claim 2, wherein the interspacer distance is periodic in the area of the uniform sample thicknessarea.
 21. The method of claim 2, wherein the multiplication product ofthe filling factor and the Young's modulus of the spacer is 2 MPa orlarger.
 22. The method of claim 2, wherein the force is applied by humanhand directly or indirectly.
 23. The method of claim 2, wherein theimprecision force applied is in the range of 1 N to 20 N.
 24. The methodof claim 2, wherein the highly uniform layer has a thickness that variesby less than 15%, 10%, or 5% of an average thickness.
 25. The method ofclaim 2, wherein the imprecise force is applied by pinching the devicebetween a thumb and forefinger.
 26. The method of claim 2, wherein theimprecision force has a variation that is at least 20% of the totalforce that actually is applied.
 27. The method of claim 2, wherein thedevice holds itself in the closed configuration after the imprecisionforce used in the pressing has been removed.
 28. The method of claim 2,wherein the uniform thickness sample layer area is larger than that areaupon which the pressing force is applied.
 29. The method of claim 2,wherein the imprecision force has a pressure in range of 0.1 kg/cm² to10 kg/cm².
 30. The method of claim 2, wherein the pressing force is notpredetermined beforehand and is not measured.
 31. The method of claim 2,wherein the analyte comprises a molecule, cells, tissues, viruses, andnanoparticles with different shapes, wherein the molecule comprises aprotein, peptides, DNA, RNA, nucleic acid, or other molecule.
 32. Themethod of claim 2, wherein the analyte comprises white blood cells, redblood cells and platelets.
 33. The method of claim 2, wherein theanalyte is stained.
 34. The method of claim 2, wherein the inter spacerdistance (ISD) is equal or less than about 120 um (micrometer).
 35. Themethod of claim 2, wherein the inter spacer distance (ISD) is equal orless than about 100 um (micrometer).
 36. The method of claim 2, whereinthe multiplication product of the filling factor and the Young's modulusof the spacer is between 20 to 150 MP.
 37. The method of claim 2,wherein the fourth power of the inter-spacer-distance (ISD) divided bythe thickness (h) and the Young's modulus (E) of the flexible plate(ISD⁴/(hE)) is 5×10⁵ um³/GPa or less.
 38. The method of claim 2, whereinthe spacers have pillar shape, a substantially flat top surface, apredetermined substantially uniform height, and a predetermined constantinter-spacer distance that is at least about 2 times larger than thesize of the analyte, wherein the Young's modulus of the spacers timesthe filling factor of the spacers is equal or larger than 2 MPa, whereinthe filling factor is the ratio of the spacer contact area to the totalplate area, and wherein, for each spacer, the ratio of the lateraldimension of the spacer to its height is at least 1 (one).
 39. Themethod of claim 2, wherein the spacers have pillar shape, a flat topsurface, a predetermined substantially uniform height, and apredetermined constant inter-spacer distance, wherein the Young'smodulus of the spacers times the filling factor of the spacers is equalor larger than 20 MPa, wherein the filling factor is the ratio of thespacer contact area to the total plate area, and wherein, for eachspacer, the ratio of the lateral dimension of the spacer to its heightis at least 1 (one), wherein the fourth power of theinter-spacer-distance (ISD) divided by the thickness (h) and the Young'smodulus (E) of the flexible plate (ISD⁴/(hE)) is 5×10⁵ um³/GPa or less,and wherein the thickness of the flexible plate times the Young'smodulus of the flexible plate is in the range of 100 to 550 GPa-um. 40.The method of claim 2, wherein the device further comprises a dryreagent coated on one or both plate.
 41. The method of claim 2, whereinthe thickness of the flexible plate times the Young's modulus of theflexible plate is in the range of 100 to 550 GPa-um.
 42. The method ofclaim 2, wherein the sample is a biological sample selected fromamniotic fluid, aqueous humour, vitreous humour, blood (e.g., wholeblood, fractionated blood, plasma or serum), breast milk, cerebrospinalfluid (CSF), cerumen (earwax), chyle, chime, endolymph, perilymph,feces, breath, gastric acid, gastric juice, lymph, mucus (includingnasal drainage and phlegm), pericardial fluid, peritoneal fluid, pleuralfluid, pus, rheum, saliva, exhaled breath condensates, sebum, semen,sputum, sweat, synovial fluid, tears, vomit, and urine.
 43. The methodof claim 2, wherein the spacers have a shape of pillars and a ratio ofthe width to the height of the pillar is equal or larger than
 2. 44. Themethod of claim 2, wherein the sample that is deposited on one or bothof the plates has an unknown volume.
 45. The method of claim 2, whereinthe sample is for the detection, purification and quantification ofchemical compounds or biomolecules that correlates with the stage ofcertain diseases.
 46. The method of claim 2, wherein the sample isrelated to infectious and parasitic disease, injuries, cardiovasculardisease, cancer, mental disorders, neuropsychiatric disorders, pulmonarydiseases, renal diseases, and other and organic diseases.
 47. The methodof claim 2, wherein the sample is related to the detection, purificationand quantification of a microorganism.
 48. The method of claim 2,wherein the sample is related to virus, fungus and bacteria from theenvironment, e.g., water, soil, or biological samples.
 49. The method ofclaim 2, wherein the sample is related to the detection, quantificationof chemical compounds or biological samples that pose a hazard to foodsafety or national security, e.g. toxic waste, anthrax.
 50. The methodof claim 2, wherein the sample is related to quantification of vitalparameters in medical or physiological monitor.
 51. The method of claim2, wherein the sample is related to glucose, blood, oxygen level, totalblood count.
 52. The method of claim 2, wherein the sample is related tothe detection and quantification of specific DNA or RNA from biosamples.53. The method of claim 2, wherein one or both plates comprise alocation marker, a scaling marker, or an image marker.
 54. The method ofclaim 2, wherein the sample is related to the detection of reactionproducts, e.g., during synthesis or purification of pharmaceuticals. 55.(canceled)
 56. The method of claim 2, wherein the sample is the samplein the detection of proteins, peptides, nucleic acids, syntheticcompounds, or inorganic compounds.
 57. The method of claim 2, whereinthe sample is the sample in the fields of human, veterinary,agriculture, foods, environments, and drug testing.
 58. The method ofclaim 2, wherein the sample is a biological sample is selected fromblood, serum, plasma, a nasal swab, a nasopharyngeal wash, saliva,urine, gastric fluid, spinal fluid, tears, stool, mucus, sweat, earwax,oil, a glandular secretion, cerebral spinal fluid, tissue, semen,vaginal fluid, interstitial fluids derived from tumorous tissue, ocularfluids, spinal fluid, a throat swab, breath, hair, finger nails, skin,biopsy, placental fluid, amniotic fluid, cord blood, lymphatic fluids,cavity fluids, sputum, pus, microbiota, meconium, breast milk, exhaledcondensate nasopharyngeal wash, throat swab, stool samples, hair, fingernail, ear wax, breath, connective tissue, muscle tissue, nervous tissue,epithelial tissue, cartilage, cancerous sample, or bone.
 59. (canceled)60. The method of claim 2, wherein the device further comprises, on oneor both plates, one or a plurality of dry binding sites and/or one or aplurality of reagent sites.
 61. The method of claim 2, wherein thespacers function as a location marker, a scale marker, an imagingmarker, or any combination thereof.
 62. The method of claim 2, whereinthe uniform thickness has a value in the range of 0.5 um to 30 um. 63.The method of claim 2, wherein the imprecision force is applied byconformal pressing.
 64. The method of claim 2, wherein the materials ofthe plate and the spacers are selected from polystyrene, PMMA, PC, COC,COP, or another plastic.